Structure Of Complex Research Articles

Studying the structure, BSA and FS-DNA interaction, fluorescence sensing of anions, cytotoxicity, and catecholase activity of Cu(II) and Zn(II) Schiff base complexes

Synthesis, characterization, X-ray crystallography, and the interaction with BSA/FS-DNA are reported for two new complexes, [{CuII2L(NCS)2}(μ1,3-NCS)]n (1) and [ZnII2L(μ1,1-N3)(N3)2] (2) (where L=[2,6-bis{N-(2-pyridylethThis section comprises references that occur in the reference list but not in the body of the text. Please position each reference in the text or, alternatively, delete it.yl)formidoyl}-4-methylphenol]). Characterization of the complexes was performed using elemental analysis, UV–vis, and FT-IR spectroscopy. X-ray analysis revealed a thiocyanate-bridged 1-D polymeric structure for complex 1 and a homodinuclear monophenoxo- and azido-bridged structure for complex 2. ‌‌Binding affinity and interaction mode with BSA/FS-DNA were investigated for both complexes using absorption and emission spectroscopy, viscosity measurement, circular dichroism, agarose gel electrophoresis, electrochemical study, and docking simulation. The EtBr replacement experiments clarified an effective binding affinity, Kb = 0.53 × 106 M−1 and Kb = 3.5 × 106 M−1 for complex 1 and 2, respectively, and intercalation as the dominant binding mode for both complexes. Furthermore, the cytotoxicity detection test of the complexes against AGS, MCF-7, PC3 cancer, and NIH/3T3 normal cell lines has shown a moderate selective anticancer activity against MCF-7 and AGS in complex 1. Both complexes triggered apoptosis-programmed cell death. Also, complex 2 showed a sensitive and selective turn-off fluorescence behavior (Kb = 1.1 × 1010 M−1) toward CrO42− among various anions with LOD of 5 × 10−7 M. Moreover, the ability of complex 1 to catalyze the oxidation of 3,5-di‑tert‑butyl catechol (3,5-DTBCH2) to its related quinone, was investigated and it showed an acceptable enzymatic activity.

Novel half-sandwich ruthenium(II) nicotinic hydrazone complexes: An efficient class of catalyst for the N-alkylation of amines with benzyl alcohol via transfer hydrogen mechanism and effective antibacterial agents

A new series of half sandwich ruthenium(II) complexes supported by nicotinic acid hydrazone derivatives of general formula [Ru(ɳ6-p-cymene)(Cl)(L)], where L represents N’-benzylidenenicotinohydrazide (HL1), N’-(naphthalen-1-ylmethylene)nicotinohydrazide (HL2) or N’-(pyren-1-ylmethylene)nicotinohydrazide (HL3) were synthesized and fully characterized. The solid-state molecular structures of ligands and complexes were elucidated with single-crystal X-ray diffraction. The ligands HL1 and HL2 possess monoclinic crystal system with P21/c and C2/c space groups respectively, whereas all the three Ru(II) complexes C1–3 are typical three-legged piano-stool geometries with orthorhombic(Aba2) (C1) and triclinic(P-1) (C2–3) systems respectively. The catalytic activities of these ruthenium complexes in the synthesis of N-alkylated amines were explored. Under optimal reaction condition, the complex C3 was found to be the most efficient catalyst for the N-alkylation of primary to secondary amines using benzyl alcohol. A wide range of substrates have been studied that includes anilines bearing electron withdrawing/electron donating group, fused aromatic, heteroaromatic, alicyclic and aliphatic amines with good to excellent yield. In addition, the antibacterial activity of the complexes were tested against different human pathogenic bacteria, among them C2 complex with naphthyl moiety was found to be the most active one against both Gram-positive (S. aureus and E. faecalis) and Gram-negative (E. coli and K. pneumoniae) bacteria. These two different studies demonstrate the catalytic and biological importance of our newly prepared Ruthenium complex.

Population genetic structure of bottlenose and whitespotted wedgefishes from the Southwest Indian Ocean using a dual marker approach

Wedgefishes (Rhinidae) are threatened by unsustainable fishing globally, and especially in the Southwest Indian Ocean (SWIO), due to their high-value fins in the shark trade. The whitespotted wedgefish Rhynchobatus djiddensis and the bottlenose wedgefish R. australiae are both classified as Critically Endangered on the IUCN Red List of Threatened Species, yet a lack of species-specific knowledge and taxonomic uncertainty still exists within this genus. Genetic approaches aid in taxonomic classification and identifying distinct populations for targeted conservation. Morphological specimen identification of samples (n = 189) collected across the SWIO was confirmed based on the cytochrome oxidase c subunit I (COI) and/or nicotinamide adenine dehydrogenase subunit 2 (ND2) gene regions. The genetic diversity and population structure within and between species and sampling locations were investigated using a dual marker approach: (1) 2 concatenated mitochondrial gene regions, namely COI and the control region (n = 117), and (2) 9 nuclear microsatellite markers (n = 146). The overall genetic diversity was moderate, with an indication that different evolutionary forces are at play on a mitochondrial versus nuclear level. The 2 species were delineated based on both marker types, and for R. djiddensis, the sampling locations of South Africa and Mozambique were genetically homogeneous. For R. australiae, significant differentiation was found between sampling locations, with Madagascar and Tanzania being genetically the most similar. This information provides critical insights into the distribution range and population structure of the whitespotted wedgefish species complex that can support the sustainable management of wedgefishes.

Structural basis of exoribonuclease-mediated mRNA transcription termination.

Efficient termination is required for robust gene transcription. Eukaryotic organisms use a conserved exoribonuclease-mediated mechanism to terminate the mRNA transcription by RNA polymerase II (PolII)1-5. Here we report two cryogenic electron microscopy structures of Saccharomyces cerevisiae PolII pre-termination transcription complexes bound to the 5'-to-3' exoribonuclease Rat1 and its partner Rai1. Our structures show that Rat1 displaces the elongation factor Spt5 to dock at the PolII stalk domain. Rat1 shields the RNA exit channel of PolII, guides the nascent RNA towards its active centre and stacks three nucleotides at the 5' terminus of the nascent RNA. The structures further show that Rat1 rotates towards PolII as it shortens RNA. Our results provide the structural mechanism for the Rat1-mediated termination of mRNA transcription by PolII in yeast and the exoribonuclease-mediated termination of mRNA transcription in other eukaryotes.

Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2.

Activation of the extracellular signal-regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named 'L' and 'R,' where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here, we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.

Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2

Activation of the extracellular signal-regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named ‘L’ and ‘R,’ where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here, we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.

HighFold: accurately predicting structures of cyclic peptides and complexes with head-to-tail and disulfide bridge constraints.

In recent years, cyclic peptides have emerged as a promising therapeutic modality due to their diverse biological activities. Understanding the structures of these cyclic peptides and their complexes is crucial for unlocking invaluable insights about protein target-cyclic peptide interaction, which can facilitate the development of novel-related drugs. However, conducting experimental observations is time-consuming and expensive. Computer-aided drug design methods are not practical enough in real-world applications. To tackles this challenge, we introduce HighFold, an AlphaFold-derived model in this study. By integrating specific details about the head-to-tail circle and disulfide bridge structures, the HighFold model can accurately predict the structures of cyclic peptides and their complexes. Our model demonstrates superior predictive performance compared to other existing approaches, representing a significant advancement in structure-activity research. The HighFold model is openly accessible at https://github.com/hongliangduan/HighFold.

Ligand Field Sensitive Spin Acceleration in the Iron-Catalyzed [2 + 2] Cycloaddition of Unactivated Alkenes and Dienes.

Redox-active pyridine(diimine) (PDI) iron catalysts promote the reversible [2 + 2] cycloaddition of alkenes and dienes to cyclobutane derivatives that have applications ranging from fuels to chemically recyclable polymers. Metallacycles were identified as key intermediates, and spin crossover from the singlet to the triplet surface was calculated to facilitate the reductive coupling step responsible for the formation of the four-membered ring. In this work, a series of sterically and electronically differentiated PDI ligands was studied for the [2 + 2] cycloaddition of ethylene and butadiene to vinylcyclobutane. Kinetic studies revealed that the fastest and slowest turnover were observed with equally electron-deficient supporting ligands that either feature phenyl-substituted imine carbon atoms (MeBPDI) or a pyrazine core (MePZDI). While the oxidative cyclization was comparatively slow for both catalysts, the rate of reductive coupling─determined by stoichiometric 13C2H4 labeling studies─correlated with the turnover frequencies. Two-state density functional theory studies and the distinct electronic structures of related (iPrBPDI) and (iPrPZDI) iron methyl complexes revealed significantly different ligand field strengths due to either diminished ligand σ-donation (MeBPDI) or promoted metal π-backbonding (MePZDI). Spin acceleration, leading to fast reductive coupling and catalytic turnover, was promoted in the case of the weaker ligand field and depends on both the nature and position of the electron-withdrawing group. This study provides strong evidence for the role of two-state reactivity in C(sp3)-C(sp3) bond formation and insights on how ligand design either promotes or inhibits spin acceleration in earth-abundant metal catalysis.

The Cyclic Imine Core Common to the Marine Macrocyclic Toxins Is Sufficient to Dictate Nicotinic Acetylcholine Receptor Antagonism.

Macrocyclic imine phycotoxins are an emerging class of chemical compounds associated with harmful algal blooms and shellfish toxicity. Earlier binding and electrophysiology experiments on nAChR subtypes and their soluble AChBP surrogates evidenced common trends for substantial antagonism, binding affinities, and receptor-subtype selectivity. Earlier, complementary crystal structures of AChBP complexes showed that common determinants within the binding nest at each subunit interface confer high-affinity toxin binding, while distinctive determinants from the flexible loop C, and either capping the nest or extending toward peripheral subsites, dictate broad versus narrow receptor subtype selectivity. From these data, small spiroimine enantiomers mimicking the functional core motif of phycotoxins were chemically synthesized and characterized. Voltage-clamp analyses involving three nAChR subtypes revealed preserved antagonism for both enantiomers, despite lower subtype specificity and binding affinities associated with faster reversibility compared with their macrocyclic relatives. Binding and structural analyses involving two AChBPs pointed to modest affinities and positional variability of the spiroimines, along with a range of AChBP loop-C conformations denoting a prevalence of antagonistic properties. These data highlight the major contribution of the spiroimine core to binding within the nAChR nest and confirm the need for an extended interaction network as established by the macrocyclic toxins to define high affinities and marked subtype specificity. This study identifies a minimal set of functional pharmacophores and binding determinants as templates for designing new antagonists targeting disease-associated nAChR subtypes.

HIPPO: HIstogram-based Pseudo-POtential for scoring protein-ssRNA fragment-based docking poses

BackgroundThe RNA-Recognition motif (RRM) is a protein domain that binds single-stranded RNA (ssRNA) and is present in as much as 2% of the human genome. Despite this important role in biology, RRM-ssRNA interactions are very challenging to study on the structural level because of the remarkable flexibility of ssRNA. In the absence of atomic-level experimental data, the only method able to predict the 3D structure of protein-ssRNA complexes with any degree of accuracy is ssRNA’TTRACT, an ssRNA fragment-based docking approach using ATTRACT. However, since ATTRACT parameters are not ssRNA-specific and were determined in 2010, there is substantial opportunity for enhancement.ResultsHere we present HIPPO, a composite RRM-ssRNA scoring potential derived analytically from contact frequencies in near-native versus non-native docking models. HIPPO consists of a consensus of four distinct potentials, each extracted from a distinct reference pool of protein-trinucleotide docking decoys. To score a docking pose with one potential, for each pair of RNA–protein coarse-grained bead types, each contact is awarded or penalised according to the relative frequencies of this contact distance range among the correct and incorrect poses of the reference pool. Validated on a fragment-based docking benchmark of 57 experimentally solved RRM-ssRNA complexes, HIPPO achieved a threefold or higher enrichment for half of the fragments, versus only a quarter with the ATTRACT scoring function. In particular, HIPPO drastically improved the chance of very high enrichment (12-fold or higher), a scenario where the incremental modelling of entire ssRNA chains from fragments becomes viable. However, for the latter result, more research is needed to make it directly practically applicable. Regardless, our approach already improves upon the state of the art in RRM-ssRNA modelling and is in principle extendable to other types of protein-nucleic acid interactions.

Visualizing Noncovalent Interactions and Property Prediction of Submicron-Sized Charge-Transfer Crystals from ab-initio Determined Structures.

The charge-transfer (CT) interactions between organic compounds are reflected in the (opto)electronic properties. Determining and visualizing crystal structures of CT complexes are essential for the design of functional materials with desirable properties. Complexes of pyranine (PYR), methyl viologen (MV), and their derivatives are the most studied water-based CT complexes. Nevertheless, very few crystal structures of CT complexes have been reported so far. In this study, the structures of two PYRs-MVs CT crystals and a map of the noncovalent interactions using 3D electron diffraction (3DED) are reported. Physical properties, e.g., band structure, conductivity, and electronic spectra of the CT complexes and their crystals are investigated and compared with a range of methods, including solid and liquid state spectroscopies and highly accurate quantum chemical calculations based on density functional theory (DFT). The combination of 3DED, spectroscopy, and DFT calculation can provide important insight into the structure-property relationship of crystalline CT materials, especially for submicrometer-sized crystals.

Phosphonate-based iron complex for a cost-effective and long cycling aqueous iron redox flow battery

A promising metal-organic complex, iron (Fe)-NTMPA2, consisting of Fe(III) chloride and nitrilotri-(methylphosphonic acid) (NTMPA), is designed for use in aqueous iron redox flow batteries. A full-cell testing, where a concentrated Fe-NTMPA2 anolyte (0.67 M) is paired with a Fe-CN catholyte, demonstrates exceptional cycling stability over 1000 charge/discharge cycles, and noteworthy performances, including 96% capacity utilization, a minimal capacity fade rate of 0.0013% per cycle (1.3% over 1,000 cycles), high Coulombic efficiency and energy efficiency near 100% and 87%, respectively, all achieved under a current density of 20 mA·cm-². Furthermore, density functional theory unveils two potential coordination structures for Fe-NTMPA2 complexes, improving the understanding between the ligand coordination environment and electron transfer kinetics. When paired with a high redox potential Fe-Dcbpy/CN catholyte, 2,2′-bipyridine-4,4′-dicarboxylic (Dcbpy) acid and cyanide (CN) ligands, Fe-NTMPA2 demonstrates a notably elevated cell voltage of 1 V, enabling a practical energy density of up to 9 Wh/L.

Geological structure and metallogeny of Precambrian sedimentary structures of western Aldan-Stanovy Shield

The article presents the results of the study by various geologists of the geological structure and prospects of ore-bearing trog complexes performing structures such as throgs, which were identified at different stages of geological research in the western part of the Aldan-Stanovy shield. The main types of traction complexes and their sections were determined. The nature of the occurrence of sedimentary (terrigenous), volcanogenicsedimentary and metavolcanic rocks performing throgs and forming throg complexes was established. The nature of the ratio of these rocks in the context of the trog complex in the studied trogs was described. The results of the study of trog complexes showed that they are generally characterized by facies variability, heterogeneity of metamorphism and dynamothermal processing of rocks (especially in the sides of trogs) with the formation of mylonites and cataclasites. It was established that the throgs are confined to three regional systems of discontinuous disturbances. Both consonantal and secant discontinuities were marked inside the throgs, defining their block tectonics. The results of determining the geological age of the rocks of the trogovoi complex were presented. The trog structures are characterized by ore mineralization associated with the processes of sedimentation (ferruginous quartzites, copper sandstones) and volcanogenic ore formation (copper-crusted and polymetallic mineralization), as well as with the processes of metamorphogenic-hydrothermal redistribution of ore matter (stratiform scheelite mineralization, ore-bearing quartz veins). It was also found that the metallogeny of the trog structures has not been studied sufficiently. Nevertheless, the majority of geologists who studied the trogovye complexes noted in their reports that Precambrian trogovye complexes can be considered as important and metallogenically promising geological objects in the western part of the Aldan-Stanovy Shield and deserve more in-depth study.

Substrate Selection Criteria in Regulated Intramembrane Proteolysis.

Alzheimer's disease is the most common form of dementia encountered in an aging population. Characteristic amyloid deposits of Aβ peptides in the brain are generated through cleavage of amyloid precursor protein (APP) by γ-secretase, an intramembrane protease. Cryo-EM structures of substrate γ-secretase complexes revealed details of the process, but how substrates are recognized and enter the catalytic site is still largely ignored. γ-Secretase cleaves a diverse range of substrate sequences without a common consensus sequence, but strikingly, single point mutations within the transmembrane domain (TMD) of specific substrates may greatly affect cleavage efficiencies. Previously, conformational flexibility was hypothesized to be the main criterion for substrate selection. Here we review the 3D structure and dynamics of several γ-secretase substrate TMDs and compare them with mutants shown to affect the cleavage efficiency. In addition, we present structural and dynamic data on ITGB1, a known nonsubstrate of γ-secretase. A comparison of biophysical details between these TMDs and changes generated by introducing crucial mutations allowed us to unravel common principles that differ between substrates and nonsubstrates. We identified three motifs in the investigated substrates: a highly flexible transmembrane domain, a destabilization of the cleavage region, and a basic signature at the end of the transmembrane helix. None of these appears to be exclusive. While conformational flexibility on its own may increase cleavage efficiency in well-known substrates like APP or Notch1, our data suggest that the three motifs seem to be rather variably combined to determine whether a transmembrane helix is efficiently recognized as a γ-secretase substrate.

Structure and digestibility of bovine casein complexes formed by enriching κ- and β-caseins in micellar casein concentrate together with minerals adjustment

Colloidal structure and infant in vitro gastrointestinal digestibility of casein complexes simulating caseins and minerals compositions of human casein micelles were studied. κ- and β-Caseins were fractionated from bovine micellar casein concentrate (MCC), and mixed with MCC to increase their ratios to 20% and 68%, followed by adding citrate (Cit), calcium (Ca), and inorganic phosphate (Pi) to obtain the casein complexes. The complexes enriched with κ- and β-caseins showed higher percentages of serum Ca, Pi and caseins, larger particle size, and looser internal structure. During gastric digestion, the complexes enriched with κ- and β-caseins formed smaller and looser coagula, which promoted degradation of intact caseins and formation of free amino groups and small peptides. During initial intestinal digestion, the complexes enriched with κ- and β-caseins formed more free amino groups and smaller peptides. These results offered a potential strategy to form human casein micelles analogues for use in infant formula.

Molecular mechanism of muscarinic acetylcholine receptor M3 interaction with Gq

Muscarinic acetylcholine receptor M3 (M3) and its downstream effector Gq/11 are critical drug development targets due to their involvement in physiopathological processes. Although the structure of the M3-miniGq complex was recently published, the lack of information on the intracellular loop 3 (ICL3) of M3 and extensive modification of Gαq impedes the elucidation of the molecular mechanism of M3-Gq coupling under more physiological condition. Here, we describe the molecular mechanism underlying the dynamic interactions between full-length wild-type M3 and Gq using hydrogen-deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cell systems. We propose a detailed analysis of M3-Gq coupling through examination of previously well-defined binding interfaces and neglected regions. Our findings suggest potential binding interfaces between M3 and Gq in pre-assembled and functionally active complexes. Furthermore, M3 ICL3 negatively affected M3-Gq coupling, and the Gαq AHD underwent unique conformational changes during M3-Gq coupling.

Modification mechanism of soybean protein isolate-soluble soy polysaccharide complex by EGCG through covalent and non-covalent interaction: Structural, interfacial, and functional properties

Soybean protein isolate was modified with polysaccharides and polyphenols to prepare a natural emulsifier with antioxidant capacity. Physicochemical, structural, interfacial, and functional properties of SPI-SSPS complex were investigated after covalent and non-covalent interacted with EGCG. SPI-SSPS-EGCG ternary complex with low EGCG concentrations (0.0625 and 0.125 mg/mL) showed a significant increase in absolute potential value and a decrease in turbidity. EGCG destroyed the original rigid structure of SPI-SSPS complex, and the covalent complexes had an ordered structure, while the non-covalent interaction resulted in disordered. The ternary complex with high EGCG concentrations (0.25 and 0.5 mg/mL) exhibited stronger EGCG binding capacity and lower surface hydrophobicity, which in turn affected its interfacial properties. The EAI and ESI of SPI-SSPS-EGCG covalent complex increased significantly, while the non-covalent complex had a significant change in EAI but no significant change in ESI with increasing EGCG concentration. The ternary complex showed significantly enhanced antioxidant capacity. The SPI-SSPS-EGCG ternary complex, with excellent antioxidant capacity and emulsifying property, making it suitable for emulsion delivery systems.

Structure of the human Bre1 complex bound to the nucleosome

Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To obtain structural insights of H2BK120 ubiquitination and its regulation, we report the cryo-electron microscopy structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0–6.5, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in two orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the H2BK120-specific ubiquitination by the Bre1 proteins and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility.

Abstract 2348: A global multiscale map of protein assemblies from integration of protein interactions and images

Abstract Cells regulate growth and function through a hierarchical structure of subcellular protein assemblies, in which alterations can result in cellular dysfunction leading to disease such as cancer. Much of this structure remains uncharted, resulting in recent efforts to map subcellular organization at different physical scales. Here, we report a global architectural map of human cancer cell protein assemblies spanning 10−9 to 10−5 nm, based on integration of near-proteome-wide affinity purification mass spectrometry-based protein interactions and immunofluorescent imaging in U-2 OS osteosarcoma cancer cells. The U-2 OS multi-scale integrated cell map places >5000 proteins into 270 distinct subcellular protein assemblies across biological scales, representing approximately half of expressed proteins. There are known organelles and protein complexes recovered in the map, as well as 152 putative assemblies, such as a putative interferon signaling complex consisting of a serine protease and STAT transcription factors. The map also incorporates 128 previously uncharacterized proteins into protein assemblies, such as C18orf21 association with a canonical RNAse complex. Protein subsystems in the U-2 OS map were evaluated for the potential for downstream integrative structural modeling, where available structural data (e.g. crosslinking, Protein Data Bank structures, AlphaFold predictions) are combined in a Bayesian framework to model the physical structures of protein complexes. Using this framework, we created an integrated structural model of new proteins interacting with the Rag-Ragulator complex, which regulates MAPK and mTOR signaling. In summary, the global proteome architecture map provides a resource for cellular biology discovery and the systematic determination of protein functions and structures. Citation Format: Leah V. Schaffer, Mengzhou Hu, Edward L. Huttlin, Gege Qian, Abantika Pal, Neelesh Soni, Andrew Latham, Laura Pontano Vaites, Trang Le, Yue Qin, Christopher Churas, Dexter Pratt, Ignacia Echeverria, Andrej Sali, J Wade Harper, Steven P. Gygi, Emma Lundberg, Trey Ideker. A global multiscale map of protein assemblies from integration of protein interactions and images [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2348.

Synthesis, characterization, and structures of mononuclear and phenoxo-/acetato-bridged trinuclear zinc(II) complexes from salan ligands: Study of their hydrolytic activity

Synthesis of one mononuclear [ZnL1] (1) and two trinuclear phenoxo-/acetato-bridged zinc(II) complexes [Zn3Cl2(L2)2] (2) and [Zn3(OAc)2(L1)2] (3) containing tetradentate diaminobis(phenolato) “salan” ligands are reported. The ligand precursors and their corresponding zinc complexes are characterized by elemental analysis, NMR, IR, and UV–vis spectroscopy. Molecular structures of complexes 2 and 3 are solved by single-crystal X-ray crystallography, while the fate of the complexes in solution is assessed by ESI-MS spectrometry analysis. All complexes (1–3) were studied for their phosphoesterase activity by using para-nitrophenyl phosphate (PNPP) and bis(2,4–dinitrophenyl) phosphate (BNPP) as substrates. While complex 1 has no activity for these substrates, complex 3 effectively hydrolyses PNPP (1.6 × 10−3 s−1), and complex 2, which is less reactive than 3, displays comparable activities towards both substrates (2.0 × 10−4 s−1 and 5.4 × 10−4 s−1, respectively). The importance of evaluating the speciation of Zn-species present for the understanding of the mechanism of the phosphoesterase reaction is discussed.