Cambridge Structural Data Research Articles

Комплексы меди [CuBr2(DMSO-O)3] и [Cu(DMSO-O)4SF6]. Синтез и строение

The dissolution of copper (II) bromide and copper (II) fluoride in the presence of hydrofluoric acid in dimethyl sulfoxide, followed by slow evaporation of the solvent, have synthesized copper complexes [CuBr 2 (DMSO- O ) 3 ] ( 1 ) and [Cu(DMSO- O ) 4 SF 6 ] ( 2 ). They have been structurally characterized. The X-ray diffraction pattern has been obtained at 293 K on an automatic diffractometer D8 Quest Bruker (Mo K α -radiation, λ = 0.71073 Å, graphite monochromator) of crystals 1 [C 6 H 18 O 3 S 3 Br 2 Cu, M 457,74, the monoclinic syngony, the symmetry group P 2 1 /c; cell parameters: a 8.812(6), b 15.335(11), c 12.272(8) Å, α = 90.00 degrees, β = 105.82(3) degrees, γ = 90,00 degrees; V = 1595.5(19)Å 3 ; the crystal size is 0.59 × 0.32 × 0,24 mm; intervals of reflection indexes are –13 ≤ h ≤ 11, –23 ≤ k ≤ 23, –18 ≤ l ≤ 18; total reflections 45529; independent reflections 5832; R int 0.0971; GOOF 1.001; R 1 = 0.0497, wR 2 = 0.1073; residual electron density 0.77/–1.36 e/Å 3 ] and 2 [C 8 H 24 O 4 F 6 S 5 Cu, M 522.11, the triclinic syngony, the symmetry group P –1; cell parameters: a 10.325(18), b 10.428(18), c 10.60(2) Å, α = 77.93(11) degrees, β = 89.49(9) degrees, γ = 68.12(6) degrees; V = 1033(3) Å 3 ; the crystal size is 0.47×0.16×0.13 mm; intervals of reflection indexes are –11 ≤ h ≤ 11, –12 ≤ k ≤ 12, –12 ≤ l ≤ 12; total reflections 9324; independent reflections 3307; R int 0.0709; GOOF 1.029; R 1 = 0.0555, wR 2 = 0.1309; residual electron density 0.64/–0.82 e/Å 3 ], the copper atoms have a distorted square-pyramidal coordination (the trans -OCuO and trans -OCuBr angles are 165.68(11)° and 143.37(10)° ( 1 ); trans -OCuO are 163.8(2), 169.0(2)° ( 2 ); the Cu-Br and Cu-O bond lengths are 2.4681(14) Å and 2.5922(14) Å ( 1 ), 1.944(3)–2.054(3) Å ( 1 ) and 1.940(6)–1.956(5) Å ( 2 ) respectively). Fragment SF 6 in 2 (the FSF trans -angles 178.8(2)–179.7(3)°, cis -angles 88.7(2)–91.0(3)°) linked to the central copper atom (the Cu–F bond length 2.208(6) Å). The structural organization of crystals 1 and 2 is controlled by intermolecular bonds O (DMSO) ∙∙∙H–С (DMSO) (2,57 Å) and Cu–Br∙∙∙H–C (DMSO) (2.89–3.04 Å) ( 1 ), S–F∙∙∙H–C (DMSO) (2.32–2.60 Å) ( 2 ). Complete tables of coordinates of atoms, bond lengths and valence angles for structures 1 and 2 are deposited at the Cambridge Structural Data Bank (no. 1883471, 1898916; deposit@ccdc.cam.ac.uk; https://www.ccdc.cam.ac.uk).

A Strong Link Between Organic Chemistry and Chemical Crystallography Started a Century Ago

The article sheds light on some historical crossings of organic chemistry and chemical crystallography. It connects past and present bringing into the focus Prof. Kata Mlinarić-Majerski’s research. An impact of structural chemistry on organic synthesis and reactivity is shown. X-ray structure analysis was established as a unique method to determine the composition and architecture of synthetic and natural organic molecules, already in the second decade of the last century; some of historical and scientific milestones are shown. Numerous controversies were solved, when intriguing molecular structures had been determined and the nature of chemical bond was clarified. An absolute structure (chirality) determination using an anomalous dispersion of X-rays was an important step forward, particularly in pharmaceutical industry. Structural data provided by X-ray crystallography, stored by Cambridge Structural Data Centre have been of great impact on many areas of science. They are closely related to intra- and intermolecular forces and structure/function correlations directing us to synthesis of compounds with designed properties. The developments of supramolecular chemistry, crystal engineering, materials science, and most of all of molecular machines have been assisted by chemical crystallography. The essay does not aim to review the complete scientific opus of Prof. K. Mlinarić-Majerski but it is focused on some of the highlights of her research. The interdisciplinary approach in her research is related to the use of X-ray structural analysis to define molecular architecture, conformational chirality, conformational isomerism, and get insight into reaction paths, interactions governing molecular assembling, and to recognise chemical properties of new compounds. In these researches the X-ray crystallographers were involved.

Синтез и строение хлоро¬(пентахлорфеноксида) трис(3-фторфенил)сурьмы (3-FC6H4)3SbCl(OC6Cl5)

Tris (3-fluorophenyl)antimony chloro(pentachlorophenoxide) ( 1 ) has been synthesized by the interaction of tris (3-fluorophenyl)antimony dichloride with tris (3-fluorophenyl)antimony bis (2,3,4,5,6-pentachlorophenoxide) (1:1 mol.) in benzene. The compound has been identified by IR spectroscopy and X-ray diffraction analysis. The absorption band of the stretching vibrations of the SbC 3 fragment at 432 cm –1 is observed in the IR spectrum of compound 1 . There is also an intensive absorption band at 1267 cm -1 , which characterizes stretching vibrations of the C-O bond. According to the X-ray diffraction analysis the coordination of the antimony atom is trigonal-bipyramidal with the chlorine and oxygen atoms in the axial positions [C 24 H 12 OCl 6 SbF 3 , M = 707.79; the triclinic system, space group P ; a 9.486(6), b 11.548(7); c 12.382(11) Å; α 73.61(2), β 87.03(3), γ 84.221(19) degrees; V 1294.2(17) Å 3 ; Z 2; µ 1.724 mm –1 ; F(000) 668.0; crystal size 0.26´0.22´0.11 mm; 2θ for data collection 5.7–62.22 degrees; index ranges −13 ≤ h ≤ 13, −16 ≤ k ≤ 16, −17 ≤ l ≤ 17; total reflections 79173; independent reflections 8254; R int 0.0560; variables 317, GOOF 1.021; R 1 = 0.0482; wR 2 = 0.1167; residual electron density 1.91/–0.56 e/Å 3 ]. The OSbCl axial angle in the molecule of compound 1 is 179.14(8)°. The sum of the CSbC angles in the equatorial plane is 360°, while the values of the individual angles vary in the interval 113.49 (15)°–126.16 (15)°. The Sb–O axial bond length is shorter than the Sb–C equatorial bond lengths and equals 2.092 (3) Å. This pattern is characteristic of most triaryl­antimony diaroxides. The formation of the compound 1 crystal structure is due to the formation of weak intermolecular contacts C–H×××Cl 2.89 Å and F×××Cl 3.08, 3.11 Å. Complete tables of coordinates of atoms, bond lengths and valence angles are deposited at the Cambridge Structural Data Bank (No. 1849662; deposit@ccdc.cam.ac.uk; http://www.ccdc. cam.ac.uk).

4-Нитрофенилацетаты тетра- и три-(пара-толил)сурьмы. Синтез и особенности строения

The interaction of penta( para -tolyl)antimony with 4-nitrophenylacetic acid in toluene have synthesized tetra( para -tolyl)antimony 4-nitrophenylacetate ( 1 ). The reaction of tri( para -tolyl)­antimony with tert -butyl hydroperoxide and 4-nitrophenylacetic acid in diethyl ether leads to the formation of tri( para -tolyl)antimony bis (4-nitrophenylacetate) ( 1 ). The X-ray diffraction pattern has been obtained at 293 K on an automatic diffractometer D8 Quest Bruker (Mo K α -radiation, λ = 0.71073 Å, graphite monochromator) of crystals 1 [C 72 H 68 N 2 O 8 Sb 2 , M 1332.78, the triclinic syngony, the symmetry group P –1; cell parameters: a 12.08(3), b 16.46(3), c 17.79(3) Å, α = 107.61(7) degrees, β = 97.20(10) degrees, γ = 101.94(9) degrees; V = 3229(11) Å 3 ; the crystal size is 0.51×0.24×0.17 mm; intervals of reflection indexes are –10 ≤ h ≤ 10, –14 ≤ k ≤ 14, –15 ≤ l ≤ 15; total reflections 14622; independent reflections 4546; R int 0.0697; GOOF 1.072; R 1 = 0.0585, wR 2 = 0.1688; residual electron density 0.75/–0.85 e/Å 3 ] and 2 [C 37 H 33 O 8 N 2 Sb, M 755.40, the monoclinic syngony, the symmetry group P2 1 /n ; cell parameters: a 9.271(2), b 28.413(7), c 13.604(3) Å, α = 90.00 degrees, β = 105.876(2) degrees, γ = 90.00 degrees; V = 3425.5(13) Å 3 ; the crystal size is 0.95×0.58×0.34 mm; intervals of reflection indexes are –16 ≤ h ≤ 16, –50 ≤ k ≤ 50, –24 ≤ l ≤ 24; total reflections 125931; independent reflections 20517; R int 0.0450; GOOF 1.114; R 1 = 0.0511, wR 2 = 0.0993; residual electron density 0.70/–0.97 e/Å 3 ] the antimony atoms have distorted trigonal-bipyramidal coordination. The axial angles of OSbC and OSbO are 177.9 (5)°, 177.9 (5) ° ( 1 ) and 177.27(5)° ( 2 ); the sum of the angles of CSbC in the equatorial plane is 356.9°, 357.6° ( 1 ), 359.79° ( 2 ). The Sb–O and Sb–C bond lengths are 2.1443(15)–2.269(10) Å and 2.098(15)–2.170(14) Å. The structural organization of crystals 1 and 2 is controlled by intermolecular bonds O···H (2.46–2.67 Å). Complete tables of coordinates of atoms, bond lengths and valence angles for structures 1 and 2 are deposited at the Cambridge Structural Data Bank (no. 1819287, 1819295; deposit@ccdc.cam.ac.uk; http: //www.ccdc. Cam.ac.uk).

Mono substituted pyrenes as multifunctional materials for OLED: Analysis of the substituent effects on the charge transport properties using DFT methods

Abstract In this work, with a general interest to understand the charge transport properties of mono substituted pyrene molecules which can be used as multifunctional materials in Organic Light Emitting Diodes (OLED), we have analyzed the charge transport properties calculated from DFT methods for a number of the mono substituted pyrene molecules whose crystal structures have been obtained from Cambridge structural data base (CSD). The data for the analysis was obtained by optimizing the geometries of the molecules in gas phase and subsequently generating the frontier orbitals and calculation of reorganization energies; transfer integrals in the solid state for various path ways were also calculated. The drift mobilities were then estimated from this data. The reasons for the variation of the drift mobilities in this group are then analyzed and the pattern reported. This work would be useful for generating new efficient pyrene derivatives and for improving existing ones for use in OLED.

Bioactive focus in conformational ensembles: a pluralistic approach.

Computational generation of conformational ensembles is key to contemporary drug design. Selecting the members of the ensemble that will approximate the conformation most likely to bind to a desired target (the bioactive conformation) is difficult, given that the potential energy usually used to generate and rank the ensemble is a notoriously poor discriminator between bioactive and non-bioactive conformations. In this study an approach to generating a focused ensemble is proposed in which each conformation is assigned multiple rankings based not just on potential energy but also on solvation energy, hydrophobic or hydrophilic interaction energy, radius of gyration, and on a statistical potential derived from Cambridge Structural Database data. The best ranked structures derived from each system are then assembled into a new ensemble that is shown to be better focused on bioactive conformations. This pluralistic approach is tested on ensembles generated by the Molecular Operating Environment's Low Mode Molecular Dynamics module, and by the Cambridge Crystallographic Data Centre's conformation generator software.

Using more than 801 296 small-molecule crystal structures to aid in protein structure refinement and analysis. Addendum.

An addendum to the Introduction of Cole et al. [(2017), Acta Cryst. D73, 234-239] is made to recognize the work of Bricogne, Smart and others in the development of methods to make use of Cambridge Structural Database data in protein structure solution.

Nitroxide stable radicals interacting as Lewis bases in hydrogen bonds: A search in the Cambridge structural data base for intermolecular contacts

1125 X-ray structures of nitroxide free radicals presenting intermolecular hydrogen bonds have been reported in the Cambridge Structural Database. We will report in this paper a qualitative and quantitative analysis of these bonds. The observation in some plots of an excluded region was statistically analyzed using convex hull and kernel smooting methodologies. A theoretical study at the MP2 level with different basis has been carried out indicating that the nitronyl nitroxide radicals (five electrons) lie just in between nitroso compounds (four electrons) and amine N-oxides (six electrons) as far as hydrogen-bond basicity is concerned.

Ferrocenyl thiocarboxylates: Synthesis, solid-state structure and electrochemical investigations

The synthesis and characterization of four ferrocenyl thiocarboxylate complexes are reported. Thus, treatment of [Fe(η5-C5H5)(η5-C5H4S−)] (1) with one equivalent of the acid chlorides 2-ClC(O)-cC4H3X(2a, X = O; 2b, X = NMe) gave [Fe(η5-C5H5)(η5-C5H4SC(O)-2-cC4H3X)] (3a, X = O; 3b, X = NMe (b)). When 1,1′-[Fe(η5-C5H4S−)2] (4) was reacted with 2-ClC(O)-cC4H3X in a 1:2 molar ratio then the respective ferrocenyl-1,1'-bis(thiocarboxylates) 1,1′-[Fe(η5-C5H4SC(O)-2-cC4H3X)2] (5a, X = O; 5b, X = NMe (b)) were produced. The solid state structures of 5a and 5b were determined by X-ray crystal structure analysis. The Crystal structure of 5a indicated the presence of oxygen…oxygen contacts, the inter-oxygen distance is 0.13 Å less than the sum of van der Waals radii. Investigation of Cambridge Structural Data base for 2-substtiuted furan molecules indicated the presence of short O…O contacts in 49 examples. Geometrical analysis of the O…O contacts indicated that the geometrical arrangement of these contacts is very similar to the well-defined C-X…X-C contacts (X = Cl, Br or I). Cyclic voltammetric studies of 3a, b and 5a, b showed reversible events at 158 and 243 mV for 3a, b and at 187 and 284 mV for 5a, b, using [NnBu4][B(C6F5)4] as the supporting electrolyte. It was found that the furyl-functionalized systems resulted in a significant higher Fc/Fc+ redox potential (E0′) as observed for the more electron-rich pyrrolyl derivatives. The Fc/Fc+ redox potential (E0′) for 5a, b is significantly higher than the one for 3a, b, due to the presence of two electron withdrawing thioester groups attached to the ferrocene in 5a, b.

NO3\u2212 anions can act as Lewis acid in the solid state

Identifying electron donating and accepting moieties is crucial to understanding molecular aggregation, which is of pivotal significance to biology. Anions such as NO3− are typical electron donors. However, computations predict that the charge distribution of NO3− is anisotropic and minimal on nitrogen. Here we show that when the nitrate’s charge is sufficiently dampened by resonating over a larger area, a Lewis acidic site emerges on nitrogen that can interact favourably with electron rich partners. Surveys of the Cambridge Structural Database and Protein Data Bank reveal geometric preferences of some oxygen and sulfur containing entities around a nitrate anion that are consistent with this ‘π-hole bonding’ geometry. Computations reveal donor–acceptor orbital interactions that confirm the counterintuitive Lewis π–acidity of nitrate.

Conformational properties of oxazoline-amino acids

Oxazoline-amino acids (Xaa-Ozn) occur in natural peptides of potentially important bioactivity. The conformations of the model compounds: Ac-(S)-Ala-Ozn(4R-Me), Ac-(S)-Ala-Ozn(4S–Me), and (gauche+, gauche−, anti) Ac-(S)-Val-Ozn(4R-Me) were studied at meta-hybrid M06-2X/6–311++G(d,p) method including solvent effect. Boc-l-Ala-l-Ozn-4-COOMe and Boc-l-Val-l-Ozn-4-COOMe were synthesized and studied by FT-IR and NMR-NOE methods. The conformations in crystal state were gathered from the Cambridge Structural Data Base. The main conformational feature of the oxazoline amino acids is the conformation β2 (ϕ,ψ ∼ −161°, −6°), which predominates in weakly polar environment and still is accessible in polar surrounding. The changes of the conformational preferences towards the conformations αR (ϕ,ψ ∼ −70°, −15°) and then β (ϕ,ψ ∼ −57°, −155°) are observed with increase of the environment polarity.

Learning about Intermolecular Interactions from the Cambridge Structural Database

A clear understanding and appreciation of noncovalent interactions, especially hydrogen bonding, are vitally important to students of chemistry and the life sciences, including biochemistry, molecular biology, pharmacology, and medicine. The opportunities afforded by the IsoStar knowledge base of intermolecular interactions to enhance the educational experience of students are summarized. Derived from experimentally determined crystal structures in the Cambridge Structural Database and Protein Data Bank, IsoStar contains geometrical and spatial information on nearly 30,000 different types of interactions in small molecules and proteins.

ChemInform Abstract: Templates for Design of Inhibitors for Serine Proteases: Application of the Program Dock to the Discovery of Novel Inhibitors for Thrombin.

The program DOCK was used to search for novel inhibitors for α-thrombin. Four among the top twelve best scoring compounds from the Cambridge Structural Data Base inhibited this enzyme, and three of them inhibited α-thrombin in a competitive mode. These molecules are expected to serve as general templates for structural elaboration in targeting diverse serine proteases for selective inhibition.

The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation

Here we describe the 1.95 A structure of the clinically used antiprogestin RU486 (mifepristone) in complex with the progesterone receptor (PR). The structure was obtained by taking a crystal of the PR ligand binding domain containing the agonist norethindrone and soaking it in a solution containing the antagonist RU486 for extended times. Clear ligand exchange could be observed in one copy of the PR ligand binding domain dimer in the crystal. RU486 binds while PR is in an agonistic conformation without displacing helix 12. Although this is probably because of the constraints of the crystal lattice, it demonstrates that helix 12 displacement is not a prerequisite for RU486 binding. Interestingly, B-factor analysis clearly shows that helix 12 becomes more flexible after RU486 binding, suggesting that RU486, being a model antagonist, does not induce one fixed conformation of helix 12 but changes its positional equilibrium. This conclusion is confirmed by comparing the structures of RU486 bound to PR and RU486 bound to the glucocorticoid receptor.

Molecular Basis of Prodrug Activation by Human Valacyclovirase, an α-Amino Acid Ester Hydrolase

Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of alpha-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific alpha-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.

An Electrostatic/Hydrogen Bond Switch as the Basis for the Specific Interaction of Phosphatidic Acid with Proteins

Phosphatidic acid (PA) is a minor but important phospholipid that, through specific interactions with proteins, plays a central role in several key cellular processes. The simple yet unique structure of PA, carrying just a phosphomonoester head group, suggests an important role for interactions with the positively charged essential residues in these proteins. We analyzed by solid-state magic angle spinning 31P NMR and molecular dynamics simulations the interaction of low concentrations of PA in model membranes with positively charged side chains of membrane-interacting peptides. Surprisingly, lysine and arginine residues increase the charge of PA, predominantly by forming hydrogen bonds with the phosphate of PA, thereby stabilizing the protein-lipid interaction. Our results demonstrate that this electrostatic/hydrogen bond switch turns the phosphate of PA into an effective and preferred docking site for lysine and arginine residues. In combination with the special packing properties of PA, PA may well be nature's preferred membrane lipid for interfacial insertion of positively charged membrane protein domains.

Reconstruction of the Complete Ouabain-binding Pocket of Na,K-ATPase in Gastric H,K-ATPase by Substitution of Only Seven Amino Acids

Although cardiac glycosides have been used as drugs for more than 2 centuries and their primary target, the sodium pump (Na,K-ATPase), has already been known for 4 decades, their exact binding site is still elusive. In our efforts to define the molecular basis of digitalis glycosides binding we started from the fact that a closely related enzyme, the gastric H,K-ATPase, does not bind glycosides like ouabain. Previously, we showed that a chimera of these two enzymes, in which only the M3-M4 and M5-M6 hairpins were of Na,K-ATPase, bound ouabain with high affinity (Koenderink, J. B., Hermsen, H. P. H., Swarts, H. G. P., Willems, P. H. G. M., and De Pont, J. J. H. H. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 11209-11214). We also demonstrated that only three amino acids (Phe(783), Thr(797), and Asp(804)) present in the M5-M6 hairpin of Na,K-ATPase were sufficient to confer high affinity ouabain binding to a chimera which contained in addition the M3-M4 hairpin of Na,K-ATPase (Qiu, L. Y., Koenderink, J. B., Swarts, H. G., Willems, P. H., and De Pont, J. J. H. H. M. (2003) J. Biol. Chem. 278, 47240-47244). To further pinpoint the ouabain-binding site here we used a chimera-based loss-of-function strategy and identified four amino acids (Glu(312), Val(314), Ile(315), Gly(319)), all present in M4, as being important for ouabain binding. In a final gain-of-function study we showed that a gastric H,K-ATPase that contained Glu(312), Val(314), Ile(315), Gly(319), Phe(783), Thr(797), and Asp(804) of Na,K-ATPase bound ouabain with the same affinity as the native enzyme. Based on the E(2)P crystal structure of Ca(2+)-ATPase we constructed a homology model for the ouabain-binding site of Na,K-ATPase involving all seven amino acids as well as several earlier postulated amino acids.

Combined quantum mechanics and molecular mechanics simulation of Ca2+/ammonia solution based on the ONIOM-XS method: Octahedral coordination and implication to biology

An extension of the ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics) method [M. Svensson, S. Humbel, R. D. J. Froese, T. Mutsubara, S. Sieber, and K. Morokuma, J. Phys. Chem. 100, 19357 (1996)] for simulation in the condensed phase, called ONIOM-XS (XS=eXtension to Solvation) [T. Kerdcharoen and K. Morokuma, Chem. Phys. Lett. 355, 257 (2002)], was applied to investigate the coordination of Ca2+ in liquid ammonia. A coordination number of 6 is found. Previous simulations based on pair potential or pair potential plus three-body correction gave values of 9 and 8.2, respectively. The new value is the same as the coordination number most frequently listed in the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). N–Ca–N angular distribution reveals a near-octahedral coordination structure. Inclusion of many-body interactions (which amounts to 25% of the pair interactions) into the potential energy surface is essential for obtaining reasonable coordination number. Analyses of the metal coordination in water, water-ammonia mixture, and in proteins reveals that cation/ammonia solution can be used to approximate the coordination environment in proteins.

High Resolution Structure of the Phosphohistidine-activated Form of Escherichia coli Cofactor-dependent Phosphoglycerate Mutase

The active conformation of the dimeric cofactor-dependent phosphoglycerate mutase (dPGM) from Escherichia coli has been elucidated by crystallographic methods to a resolution of 1.25 A (R-factor 0.121; R-free 0.168). The active site residue His(10), central in the catalytic mechanism of dPGM, is present as a phosphohistidine with occupancy of 0.28. The structural changes on histidine phosphorylation highlight various features that are significant in the catalytic mechanism. The C-terminal 10-residue tail, which is not observed in previous dPGM structures, is well ordered and interacts with residues implicated in substrate binding; the displacement of a loop adjacent to the active histidine brings previously overlooked residues into positions where they may directly influence catalysis. E. coli dPGM, like the mammalian dPGMs, is a dimer, whereas previous structural work has concentrated on monomeric and tetrameric yeast forms. We can now analyze the sequence differences that cause this variation of quaternary structure.

Effects of electron correlation and the environment on the conformational preferences of the β-alanine dipeptide

The conformational preferences of the β-alanine dipeptide have been determined in the gas-phase using HF/6-31G(d) and MP2/6-31G(d) geometry optimizations. The conformational energy of the six resulting minima was estimated by single point calculations at both the HF/6-311G(d,p) and MP2/6-311G(d,p) levels. Self-consistent reaction field calculations using the polarizable continuum method were performed in order to evaluate the effect of the solvent on the relative stability of the different minima. Furthermore, the theoretical results obtained for the dipeptide have been compared with the conformational preferences found for the β-alanine residue in small peptides by examination of the Cambridge Structural Data Base. The influence of both electron correlation and the environment on the conformational energies is discussed.