Monophosphate Complexes Research Articles

Structural changes at the metal ion binding site during the phosphoglucomutase reaction.

An electron density map of the reactive, Cd2+ form of crystalline phosphoglucomutase from X-ray diffraction studies shows that the enzymic phosphate donates a nonbridging oxygen to the ligand sphere of the bound metal ion, which appears to be tetracoordinate. 31P and 113Cd NMR spectroscopy are used to assess changes in the properties of bound Cd2+ produced by substrate/product and by substrate/product analog inhibitors. The approximately 50 ppm downfield shift of the 113Cd resonance on formation of the complex of dephosphoenzyme and glucose 1,6-bisphosphate is associated with the initial sugar-phosphate binding step and likely involves a change in the geometry of the coordinating ligands. This interpretation is supported by spectral studies involving various complexes of the active Co2+ and Ni(2+)-enzyme. In addition, there is a loss of the 31P-113Cd J coupling that characterizes the monophosphate complexes of the Cd2+ enzyme either during or immediately after the PO3- transfer step that produces the bisphosphate complex, indicating a further change at the metal binding site. The implications of these observations with respect to the PO3- transfer process in the phosphoglucomutase reaction are considered. The apparent plasticity of the ligand sphere of the active site metal ion in this system may allow a single metal ion to act as a chaperone for a nonbridging oxygen during PO3- transfer or to allow a change in metal ion coordination during catalysis. A general NMR line shape/chemical-exchange analysis for evaluating binding in protein-ligand systems when exchange is intermediate to fast on the NMR time scale is described. Its application to the present system involves multiple exchange sites that depend on a single binding rate, thereby adding further constraints to the analysis.

X-Ray Structural Studies of Metal-Nucleoside and Metal-Nucleoside Monophosphate Complexes: New Perspectives

Abstract The X-ray structures of metal-nucleoside and metal-nucleoside monophosphate complexes published from 1980 to the end of 1991 are examined and classified. The first 3d trans bis divalent me...

Electronic structure determination and dynamical properties of iron (II)-guanosine-5′-monophosphate complex via mossbauer and magnetic susceptibility measurements

The electronic structure of the ferrous ion in the Fe(II)-5′-GMP complex has been determined by means of least-squares fittings of the temperature dependence of both the quadrupole splitting and the magnetic susceptibility experimental data, using a crystal-field approximation. The resulting low lying energy levels in order of increasing energy were 5B2, 1A1, 5E, and 3E, but after applying the rhombic perturbation, the rhombic-split 5E term became the ground state due to a quite large rhombic distortion D=−2236 cm−1. The set of crystal-field parameters obtained from the fit has been correlated with the molecular structure of the Fe(II)-5′-GMP derivative. The great value of the ε2 parameter is indicative of a strong N7–Fe interaction while the values of the ε3 parameter and the rhombic distortion are in agreement with a large distortion in the octahedron plane. Finally, the Debye temperature of the solid has been derived from the thermal variation of the Lamb–Mössbauer factor and has been used to calculate the second-order Doppler shift of the ferrous cation which, together with the assumption of a linear temperature dependence for the intrinsic isomer shift, reproduces the isomer shift experimental data.

Metal‐ion‐governed molecular recognition: extent of intramolecular stack formation in mixed‐ligand–copper(II) complexes containing a heteroaromatic N base and an adenosine monophosphate (2′AMP, 3′AMP, or 5′AMP)

Stability constants of mixed-ligand Cu(Arm)(AMP) complexes [where Arm = 2,2'-bipyridyl (Bpy) or 1,10-phenanthroline (Phen) and AMP2- = 2'AMP2-, 3'AMP2- or 5'AMP2-] were determined by potentiometric pH titrations in aqueous solution at I = 0.1 M (NaNO3) and 25 degrees C. The ternary Cu(Arm)(AMP) complexes are more stable than corresponding Cu(Arm)(R-MP) complexes, where R-MP2- represents a phosphate monoester with a group R that is unable to participate in any kind of interaction within the complexes as, for example, D-ribose 5'-monophosphate. This increased stability is attributed, in agreement with previous results, to intramolecular stack formation in the Cu(Arm)(AMP) complexes between the purine residue of the AMPs and the aromatic rings of Bpy or Phen. Based on correlation lines (previously obtained from log K versus pKa plots) for Cu(Arm)(R-MP) complexes without a ligand-ligand interaction, a quantitative evaluation was carried out. The degree of formation of the species with the intramolecular stacks increases for the Cu(Arm)(AMP) complexes in the series: 3'AMP2- less than 5'AMP2- less than 2'AMP2-; e.g. in Cu(Bpy)(3'AMP) the stack reaches a formation degree of 45 +/- 11% and in Cu(Bpy)(2'AMP) one of 96.1 +/- 0.7% is obtained. It must be emphasized that these differences are due to the different steric orientations of the bridging metal ion, which result from the varying position of the phosphate group on the ribose ring. As shown by 1H-NMR shift measurements, there is no significant effect of the position of the phosphate group on the stability of the binary (Phen)(AMP)2- adducts (K approximately 36 M-1 in D2O); such an effect is seen only if a metal-ion bridge is formed between the moieties forming the stack, i.e. metal-ion coordination imposes individual properties on the AMPs. By also taking into account some recent results on other nucleoside 5'-monophosphate complexes, the following trend for an increasing stacking tendency of the nucleic base moieties can be established: uracil approximately less than cytosine approximately less than thymine much less than adenine less than 7-deazaadenine. Some additional conclusions of general importance are given and the relevance of the results with regard to bio-systems is indicated.

Computer modeling studies of ribonuclease T1–guanosine monophosphate complexes

The three-dimensional structures of ribonuclease (RNase) T1 complexes with the inhibitors 2'-guanylic acid (2'-GMP), 3'-guanylic acid (3'-GMP), and 5'-guanylic acid (5'-GMP) were predicted by energy minimization studies. It is shown that these inhibitors can bind to RNase T1 in either of the ribose puckered conformations (C2'-endo and C3'-endo) in solid state and exist in significant amounts in both forms in solution. These studies are in agreement with the x-ray crystallographic studies of the 2'-GMP-Lys25-RNase T1 complex, where the inhibitor binds in C2'-endo puckered conformation. These results are also in good agreement with the available 1H-nmr results of Inagaki et al. [(1985) Biochemistry 24, 1013-1020], but differ from their conclusions where the authors favor only the C3'-endo ribose conformation for all the three inhibitors. The calculations explain the apparent discrepancies in the conclusions drawn by x-ray crystallographic and spectroscopic studies. An extensive hydrogen-bonding scheme was predicted in all the three complexes. The hydrogen-bonding scheme predicted for the 2'-GMP (C2'-endo)-RNase T1 complex agrees well with those reported from x-ray crystallographic studies. In all three complexes the base and the phosphate bind in nearly identical sites independent of the position of the phosphate or the ribose pucker. The glycosyl torsion angle favors a value in the +syn range in the 2'-GMP (C2'-endo)-RNase T1, 3'-GMP (C2'-endo)-RNase T1, and 3'-GMP (C3'-endo)-RNase T1 complexes; in the high-syn range in the 2'-GMP (C3'-endo)-RNase T1 complex; and in the -syn range in the 5'-GMP (C2'-endo)-RNase T1 and 5'-GMP (C3'-endo)-RNase T1 complexes. These results are in agreement with experimental studies showing that the inhibitory power decreases in the order 2'-GMP greater than 3'-GMP greater than 5'-GMP, and they also explain the high pKa value observed for Glu58 in the 2'-GMP-RNase T1 complex.

Structure and stabilities of bivalent metal-xanthosine monophosphate complexes in solution

Structure and stabilities of bivalent metal-xanthosine monophosphate complexes in solution

A theoretical investigation of the intercalative binding of 7-H pyrido[4.3C]carbazole chromophore into a d(CpG)2 minihelix.

Theoretical computations are performed of the intercalative binding to a model d(CpG)2 minihelix of 7-H pyrido[4.3C]carbazole, the precursor of the antitumor bisintercalating drug ditercalinium. The conformations of the intercalation site are generated by the AGNAS procedure (algorithm to generate nucleic acid structures) of Miller and co-workers. The ligand-nucleotide interactions and the nucleotide conformational energies are computed with the SIBFA procedures (sum of interactions between fragments ab initio computed), which use formulas of empirical origin that reproduce ab initio SCF (self-consistent field) computations. Among the candidate intercalation sites most favored energetically, one has a pattern of conformational angles related to the one determined crystallographically by Sobell et al. in a series of x-ray structural studies of small intercalator-dinucleotide monophosphate complexes. Optimal values of the unwinding angle, found in the range of -12 degrees to -14 degrees, are consistent with available experimental data on DNA.

核酸の分子構造及び核酸・蛋白質相互作用機構についてのX線解析法による構造研究

Since the discovery of the right-handed double helical structure of deoxyribonucleic acid by Watson and Crick in 1953, many pieces of detailed nucleic acid structural information involving ribonucleic acid have been elucidated and this review describes the results of the X-ray structural studies of nucleic acids and their constituents carried out in my laboratory. In the latter half the nucleic acid-protein interaction mechanism was also discussed on the basis of the molecular model of the stacking interaction between base and aromatic amino acid side chains. The structure-function relationship of ribonuclease T1.guanosine monophosphate complex was used as an example.

Purine nucleotide-metal complexes

Some results of structural studies on metal- purine nucleotide compounds are presented. The X-ray analysis of a new crystalline form of a copper(II)- inosine monophosphate complex reveals interesting conformational features in the nucleoside moieties. The ‘phosphate only’ binding mode seems to be the preferred one for ternary complexes of Mg(II), Ca(II), Mn(II), Co(II), Cu(II) and Zn(II) and purine nucleotide. The molecular structure already found in Mg(II), Ca(II), Mn(II) and Co(II)-ATP (adenosine 5′-triphosphate) complexes consisting of M(ATP) 2 units does not seem favorable for the Cu(II) cation.

Stacking and hydrogen bonding interactions between phenylalanine and guanine nucleotide: Crystal structure of L-phenylalanine-7-methylguanosine-5′-monophosphate complex

The crystal structure of title complex has been analyzed by X-ray diffraction method as a model for elucidating the possible interaction between the phenylalanyl residue of proteins and the N7-protonated or methylated guanine base of nucleic acids. The guanine base is associated with the benzene ring of phenylalanine by stacking interaction, and further connected with the carboxyl group by the formation of a pair of hydrogen bonds. These two interaction modes are suggested to be responsible for the specific recognition of base sequence by protein.

Magnesium – nucleotide interaction. Synthesis, structure, 1H, 13C nuclear magnetic resonance and Fourier transform infrared studies of Mg-inosine-5′-monophosphate complexes

The reaction of inosine-5′-monophosphate acid (IMPH2) with hydrated magnesium chloride MgCl2•6H2O gives complexes of the type Mg(IMP)•5H2O and Mg2(IMP)3•15H2O. The FT-IR spectra of Mg(IMP)•5H2O in the region 1800–400 cm−1 showed marked similarities with that of the structurally characterized N7-bound Ni(IMP)•5H2O and Co(IMP)•5H2O complexes, while Mg2(IMP)3•15H2O exhibited distinct spectral similarities with the known Cd2(IMP)3•12H2O and Ca(IMP)•6.5H2O compounds, where a direct metal–phosphate and metal–sugar binding as well as metal–N7-coordination has been shown crystallographically. The Mg(II) ion in Mg(IMP)•5H2O is N7-bound with an indirect metal–phosphate and metal–carbonyl interaction through a coordinated water molecule and in the Mg2(IMP)3•15H2O compound it binds directly to the phosphate and to the sugar moiety as well as to the N7-site of the purine ring system.

Adenosine-5′-monophosphate complexes of Pt(II) and Mg(II) metal ions. Synthesis, FTIR spectra and structural studies

Several complexes of Pt(II) and Mg(II) metal ions with adenosine-5′-monophosphate have been isolated. The complexes are of the formulae cis and trans-[Pt(L) 2(NH 3) 2]Cl 2·xH 2O, Pt(L) nCl 2·xH 2O and Mg(L′)·xH 2O, where n = 1, 2, 3, x = 5, 6–10 and L = disodium salt of adenosine-5′-monophosphate (5′-AMPNa 2) and L′ = adenosine-5′-monophosphate dianion (AMP 2−). Due to the distinct spectral similarities with the structurally known N 7-bonded Ni(5′-AMP)·6H 2O, the mononucleotide binds to Pt(II) and Mg(II) ions through the N 7-atom of the purine ring system. No direct metalphosphate interaction was observed for the platinum(II) complexes synthesized here. The MgAMP compounds showed direct Mgphosphate interaction if prepared at acidic pH and no direct Mgphosphate bonding was observed when prepared at neutral or slightly basic pH values.

X-ray crystallographic and nuclear magnetic resonance spectral studies of the products from the yeast inorganic pyrophosphatase-Co(NH3)4PP reaction. Investigation of the pyrophosphatase reaction mechanism.

Yeast inorganic pyrophosphatase catalyzes the hydrolysis of P1,P2-bidentate Co(NH3)4 pyrophosphate [Co(NH3)4PP] to the cis, bis(phosphate) complex Co(NH3)4(Pi)2, which is not stable at neutral pH and over a period of 24 h converts to HPO4(2-) and a mixture of bidentate Co(NH3)4(PO4) and monodentate Co(NH3)4(H2O)(HPO4). Concurrent with this process is the reduction and subsequent release of Co(H2O)6(2+) from the cobalt tetraammine bis(phosphate) complex and/or the cobalt tetraammine monophosphate complex. Bidentate tetraammine phosphatocobalt (III), hexaaquocobalt(II), orthophosphate, and two free water molecules cocrystallize [Co(NH3)4PO4 . Co(H2O)6(2+) . HPO4(2-) . 2H2O] from the reaction mixture in the triclinic space group Pi (Z = 2) with cell dimensions a = 6.849 (1) A, b = 11.693 (2) A, c = 12.630 (2) A, alpha = 65.60 (1) degree, beta = 88.98 (1) degree, and gamma = 73.04 (1) degree. The structure was solved by the heavy atom technique and refined to an R index of 0.040 by using 3077 intensities measured up to a 2 theta limit of 155 degrees. 31P NMR studies of the equilibrium mixture reveal that the equilibrium constant is a sensitive function of solution pH and temperature. Unlike the Co(NH3)4PP complex, there is evidence indicating that the Mg(H2O)4PP complex is degraded to monodentate Mg(H2-O)5PO4 in the enzyme active site.

Proton magnetic resonance analysis of terbium ion-nucleic acid complexes: Further evidence for two-site binding to polynucleotides

Terbium ion (Tb 3+), like other rare earth lanthanides, has traditionally been viewed as binding nucleic acids at or near their ionized phosphate groups only. Here evidence is presented from 1H NMR studies that confirms this mode of binding in Tb 3+- mono-nucleotide complexes. However, in polynucleotides, we find that Tb 3+ coordinately binds at two distinct sites, the phosphate moiety and electron donor groups on purine and pyrimidine bases. This two-site binding is best illustrated by complexes of Tb 3+-polyuridylic acid, where the relative sensitivities of the uracil protons H5 and H6 to induced chemical shift and nuclear spin relaxation are the inverse of that seen in Tb 3+-uridine monophosphate complexes. These data substantiate recently reported results derived from ultraviolet absorption and fluorescence spectroscopy ( D. S. Gross and H. Simpkins, 1981, J. Biol. Chem. 256, 9593–9598 ) that two-site binding is characteristic of the terbium(III)-polynucleotide interaction.

ChemInform Abstract: LANTHANIDE ETHYLENEDIAMINETETRAACETATE CHELATES AS AQUEOUS SHIFT REAGENTS: EVIDENCE FOR EFFECTIVE AXIAL SYMMETRY IN BIDENTATE CYTIDINE 5′‐MONOPHOSPHATE AND ALANINE COMPLEXES

Chemischer InformationsdienstVolume 13, Issue 4 Organoelement Compounds ChemInform Abstract: LANTHANIDE ETHYLENEDIAMINETETRAACETATE CHELATES AS AQUEOUS SHIFT REAGENTS: EVIDENCE FOR EFFECTIVE AXIAL SYMMETRY IN BIDENTATE CYTIDINE 5′-MONOPHOSPHATE AND ALANINE COMPLEXES A. D. SHERRY, A. D. SHERRYSearch for more papers by this authorC. A. STARK, C. A. STARKSearch for more papers by this authorJ. R. ASCENSO, J. R. ASCENSOSearch for more papers by this authorC. F. G. C. GERALDES, C. F. G. C. GERALDESSearch for more papers by this author A. D. SHERRY, A. D. SHERRYSearch for more papers by this authorC. A. STARK, C. A. STARKSearch for more papers by this authorJ. R. ASCENSO, J. R. ASCENSOSearch for more papers by this authorC. F. G. C. GERALDES, C. F. G. C. GERALDESSearch for more papers by this author First published: January 26, 1982 https://doi.org/10.1002/chin.198204272Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume13, Issue4January 26, 1982 RelatedInformation

Conformational characteristics of dimeric subunits of RNA from energy minimization studies. Mixed sugar-puckered ApG, ApU, CpG, and CpU

Following the procedure described in the preceding article, the low energy conformations located for the four dimeric subunits of RNA, ApG, ApU, CpG, and CpU are presented. The A-RNA type and Watson-Crick type helical conformations and a number of different kinds of loop promoting ones were identified as low energy in all the units. The 3E-3E and 3E-2E pucker sequences are found to be more or less equally preferred; the 2E-2E sequence is occasionally preferred, while the 2E-3E is highly prohibited in all the units. A conformation similar to the one observed in the drug-dinucleoside monophosphate complex crystals becomes a low energy case only for the CpG unit. The low energy conformations obtained for the four model units were used to assess the stability of the conformational states of the dinucleotide segments in the four crystal models of the tRNAPhe molecule. Information on the occurrence of the less preferred sugar-pucker sequences in the various loop regions in the tRNAPhe molecule has been obtained. A detailed comparison of the conformational characteristics of DNA and RNA subunits at the dimeric level is presented on the basis of the results.

13C NMR investigations on the stacking of 5'-AMP with tryptamine.

Complex formation between 5'-adenosine monophosphate (5'-AMP) and tryptamine was investigated by measuring 13C chemical shifts and spin-lattice relaxation times. The chemical shift changes observed were attributed to ring current effects originating in the stacking of the two respective aromatic moieties and to puckering changes of the AMP ribose. Differences in the magnitude of the shifts of the aromatic carbons were related to the geometry of the complex and compared with those found for AMP selfassociation. Upon complex formation the relaxation times of especially the tryptamine indole carbons were greatly reduced, this was explained by an increase in the particle size. Small changes found for the AMP carbons in solutions without tryptamine result from AMP selfassociation. Deviations from isotropic motion observed for the non-aromatic moieties are discussed.

Evidence for sequence preferences in the intercalative binding of ethidium bromide to dinucleoside monophosphates

The formation of solution complexes of ethidium bromide with the self-complementary ribodinucleoside monophosphates, as well as ethidium complexes with mixtures of complementary and non-complementary ribodinucleoside monophosphates, has been monitored by circular dichroism, fluorescence, nuclear magnetic resonance, and visible spectroscopic techniques. Although ethidium bromide will form a complex with all of the dinucleoside monophosphates used in this study, it does exhibit a definite preference for binding to dinucleosides that have a pyrimidine (3′-5′) purine sequence when compared to their isomeric purine (3′-5′) pyrimidine sequence dinucleosides. The pyrimidine-purine sequence dinucleoside monophosphate complexes with ethidium exhibit fluorescence, circular dichroism, and visible spectra that closely resemble the spectra observed for the ethidium complexes with double-stranded nucleic acids. An analysis of the nuclear magnetic resonance spectra of the same ethidium-dinucleoside monophosphate solutions used for the optical experiments shows that complexation results in the formation of a miniature double-helical complex in which the phenanthridinium ring of ethidium bromide is intercalated between the adjacent base-pairs of a miniature double-helical complex. The formation of a double-helical complex is also indicated by the observation of the hydrogen-bonded guanine ring NH resonance in a complex of ethidium bromide with CpG dissolved in an aqueous solution. The combination of the optical spectroscopies and the nuclear magnetic resonance experiments on these model systems thus provides direct evidence for the intercalation model for the binding of ethidium bromide to double-stranded nucleic acids. The fact that ethidium preferentially interacts with dinucleoside monophosphate sequence isomers suggests that it binds to the various base sequences available as intercalation sites on DNA and RNA with significantly different binding constants.

Ternary complexes in solution. XIV. The stability increasing effect of the pyridyl and imidazole groups on the formation of mixed amine-copper(II)-adenosine 5'-monophosphate complexes.

The stability constants of the ternary Cu2+ complexes containing adenosine 5′-monophosphate (AMP) and as a second ligand, 2,2′-bipyridyl, 4- (2′-pyridyl) imidazole, 2-picolylamine, 4-aminomethylimidazole, and ethylenediamine were determined by potentiometric titration in water containing 10% dioxane (I=0.1; 25°C). For the equilibrium, Cu (amine) 2++Cu (AMP) ⇄Cu (amine) (AMP) +Cu2+, the corresponding constants are (in the order of the above amine ligands), Δ log K =log = 0.53, 0.20, 0.04, —0.35, and —0.45; hence, in the first cases the equilibrium is considerably on the side of the mixed-ligand complex. The importance of the π-system of the amine for the stability of the mixed-ligand Cu2+ complexes is obvious from the given series. The imidazole group, an important binding site for metal ions in biological systems, has clearly qualities similar to the pyridyl group (Inorg. Chem. 9, 1238 [1970]), i. e. the stability of ternary Cu2+ complexes containing these groups is increased.

Fructose diphosphatase from rabbit muscle: III. Isolation of enzyme-substrate and enzyme-adenosine monophosphate complexes

The binding of substrate (fructose diphosphate) and allosteric effector (AMP) to purified rabbit muscle fructose diphosphatase has been measured at pH 7.5 and at pH 9.3. The enzyme contains approximately four binding sites for each of these ligands. The saturation curve for the formation of the enzyme-substrate complex at pH 7.5 is sigmoidal, suggesting a cooperative interaction between binding sites. The values of the microscopic association constants at this pH range from 3.0 × 10 5 m −1 to 3.5 × 10 6 m −1. The muscle enzyme has a lower affinity for the substrate than does the liver enzyme. The binding of AMP to muscle fructose diphosphatase at neutral pH is not affected by substrate or Mg 2+. The saturation curve at pH 7.5 is hyperbolic and the association constant for the enzyme-AMP complex is 1.2 × 10 6 m −1. In the presence of Mn 2+, however, there is evidence for a positive interaction between the AMP-binding sites. The affinity of the muscle enzyme for AMP is approximately 20 times greater than that of the liver enzyme.