Papers by Gábor Náray/Szabó
Abstract. Molecular recognition is a key process in non-covalent interactions, which determines, ... more Abstract. Molecular recognition is a key process in non-covalent interactions, which determines, among others, host-guest complexation, drug action and protein-protein interaction. A simple and attractive for-mulation is the lock-and-key analogy defining the host as a lock accommodating the guest as a key. We stress three major aspects of molecular recognition, determining both complementarity between host and guest and similarity within a group of guest molecules. These aspects are: steric, i.e. maximization of close contacts, electrostatic, i.e. maximization of electrostatic attraction between host and guest, as well as hydrophobic, i.e. avoiding hydrophobic hydration, which can be reached by the maximization of apolar contacts between interacting molecules. Some examples are presented from our laboratory: the complexes of acylaminoacyl peptidase with small peptides, the effect of heparin binding on inhibitory potency of C1-inhibitor as well as small-molecule ligand binding to pro...
In this paper we extend our theoretical studies dealing with the dependence of relative proton an... more In this paper we extend our theoretical studies dealing with the dependence of relative proton and carbon chemical shifts (CSs) of protein backbone atoms on their conformational position. In an earlier paper (A. Czajlik, I. Hudaky, A. Perczel, J Comp Chem 2011, 32, 3362) we reported on a fair agreement between calculated and observed backbone CSs as a function of backbone conformation. Applying the polarizable continuum model (PCM) in this work, we compare relative CSs of fully optimized alanine diamide conformers with gas phase calculations and experimental results. Along a path on the Ramachandran surface, we collated calculated relative CSs obtained with and without explicit water molecules, as well as with and without considering the PCM reaction field. Furthermore, we traced the energetically relevant reaction paths along the torsional angle ψ connecting the lowest energy minima (helical, extended, polyproline II and inverse γ-turn) on the Ramachandran plot, with the prospect t...
Acta Crystallographica Section A Foundations of Crystallography, 1996
The following versions of software and data (see references i ○) were used in the production of t... more The following versions of software and data (see references i ○) were used in the production of this report:
ACS Symposium Series, 1999
Current Computer Aided-Drug Design, 2009
Calmodulin plays a role in several life processes, its flexibility allows binding of a number of ... more Calmodulin plays a role in several life processes, its flexibility allows binding of a number of different ligands from small molecules to amphiphilic peptide helices and proteins. Through the diversity of its functions, it is quite difficult to find new drugs, which bind to calmodulin as a target. We present available structural information on the protein, obtained by X-ray diffraction, nuclear magnetic resonance spectroscopy and molecular modeling and try to derive some conclusions on structureactivity relationships.
Virology, 2007
The Ns strain of Cucumber mosaic virus (CMV) induces hypersensitive response (HR) on Nicotiana ta... more The Ns strain of Cucumber mosaic virus (CMV) induces hypersensitive response (HR) on Nicotiana tabacum cv. Xanthi-nc and on Nicotiana glutinosa. The genetic determinant of the HR induction was localized earlier to amino acid 461 of the 1a protein. The 3D structure of the 1a protein is still unknown and building a homology model is impossible. Nevertheless, on the basis of secondary structure predictions we have created partial protein models for the region surrounding residue 461 which can account structurally for the effect of aa 461 on elicitor function. Seven different amino acid mutations were designed and introduced to the position 461 of the 1a protein in RNA 1. Three of the mutations (proline, glutamic acid, asparagine) inhibited virus replication. Two of the mutants caused systemic symptom development (lysine and arginine). Two mutants (alanine and serine) resulted in localization of the virus, but strong necrosis similar to the original Ns-CMV strain was not observed. Inoculation of purified Ns-CMV virions at extremely high concentration provoked systemic symptoms.
European Journal of Biochemistry, 1999
has played an important role in recent studies on the structural basis of substrate-specific cata... more has played an important role in recent studies on the structural basis of substrate-specific catalysis by serine proteases. The present work reports the three-dimensional structure of this mutant crystallized in unliganded form: the first unliganded rat trypsin structure reported. The X-ray structure of the Asp189Ser trypsin mutant in complex with bovine pancreatic trypsin inhibitor is already known. The X-ray structure of free Asp189Ser rat trypsin revealed that the single amino acid mutation at the bottom of the substrate binding pocket of trypsin resulted in extensive structural changes around the mutated site and in dimerization of the mutant, in contrast with the complexed enzyme the structure of which is practically the same as that of wild-type trypsin. The structural rearrangement in the mutant was shown to be restricted to the activation domain region providing further evidence for the allosteric property of this structural±functional unit of the enzyme. This study supports our view that the plasticity of the activation domain may play an important role in the mechanism of substratespecific serine protease action.
Proceedings of the National Academy of Sciences, 1988
The aspartic residue (Asp-189) at the base of the substrate-binding pocket of trypsin was replace... more The aspartic residue (Asp-189) at the base of the substrate-binding pocket of trypsin was replaced by serine (present in a similar position in chymotrypsin) through site-directed mutagenesis. The wild-type (with Asp-189 in the mature trypsin sequence) and mutant (Ser-189) trypsinogens were expressed in Escherichia coli, purified to homogeneity, activated by enterokinase, and tested with a series of fluorogenic tetrapeptide substrates with the general formula succinyl-Ala-Ala-Pro-Xaa-AMC, where AMC is 7-amino-4-methyl-coumarin and Xaa is Lys, Arg, Tyr, Phe, Leu, or Trp. As compared to [Asp189]trypsin, the activity of [Ser189]trypsin on lysyl and arginyl substrates decreased by about 5 orders of magnitude while its Km values increased only 2- to 6-fold. In contrast, [Ser189]trypsin was 10-50 times more active on the less preferred, chymotrypsin-type substrates (tyrosyl, phenylalanyl, leucyl, and tryptophanyl). The activity of [Ser189]trypsin on lysyl substrate was about 100-fold great...
Journal of Molecular Biology, 2003
The crystal structure of S189D rat chymotrypsin have been determined (resolution 2.55 Å) and comp... more The crystal structure of S189D rat chymotrypsin have been determined (resolution 2.55 Å) and compared, together with D189S rat trypsin to wild-type structures to examine why these single mutations resulted in poorly active, non-specific enzymes instead of converting the specificities of trypsin and chymotrypsin into each other. Both mutants have stable structure but suffer from a surprisingly large number of serious deformations. These are restricted to the activation domain, mainly to the substrate-binding region and are larger in S189D chymotrypsin. A wild-type substrate-binding mode in the mutants is disfavored by substantial displacements of the Cys191-Cys220 disulfide and loop segments 185-195 (loop C2/D2) and 217-224 (loop E2/F2) at the specificity site. As a consequence, the substrate-binding clefts become wider and more solventaccessible in the middle third and occluded in the lower third. Interestingly, while the Ser189 residue in D189S trypsin adopts a chymotrypsinlike conformation, the Asp189 residue in S189D chymotrypsin is turned out toward the solvent. The rearrangements in D189S trypsin are at the same sites where trypsin and trypsinogen differ and, in S189D chymotrypsin, the oxyanion hole as well as the salt-bridge between Asp194 and the N-terminal of Ile16 are missing as in chymotrypsinogen. Despite these similarities, the mutants do not have zymogen conformation. The Ser189Asp and Asp189Ser substitutions are structurally so disruptive probably because the stabilization of such a different specificity site polarities as those after the removal or introduction of a charged residue are beyond the capability of the wild-type conformation of the substratebinding region.
Journal of Computational Chemistry, 1987
Computer programs have been developed or are under development for the IBM personal computer that... more Computer programs have been developed or are under development for the IBM personal computer that enable their users to get information on atomic charges, electrostatic potentials, conformational and other properties of molecular systems containing H, C, N, O, F, Si, P, S, or Cl atoms. The zero‐order wavefunction is constructed of strictly localized molecular orbitals with fixed atomic orbital coefficients. The wave function can be refined by optimizing these coefficients, i.e., considering inductive effects via a coupled set of 2 × 2 secular equations within the CNDO/2 approximation. Delocalization and exchange effects are accounted for by expanding the wavefunction on a basis of the aforementioned strictly localized orbitals, instead of conventional atomic orbitals, and solving the corresponding SCF equations. Our method has been applied to the study of large systems. We calculated the electrostatic field of the complex of β‐trypsin and basic pancreatic trypsin inhibitor and it ha...
CLCWeb: Comparative Literature and Culture, 2014
Dedicated to the dissemination of scholarly and professional information, Purdue University Press... more Dedicated to the dissemination of scholarly and professional information, Purdue University Press selects, develops, and distributes quality resources in several key subject areas for which its parent university is famous, including business, technology, health, veterinary medicine, and other selected disciplines in the humanities and sciences. CLCWeb: Comparative Literature and Culture, the peer-reviewed, full-text, and open-access learned journal in the humanities and social sciences, publishes new scholarship following tenets of the discipline of comparative literature and the field of cultural studies designated as "comparative cultural studies.
Acta Crystallographica Section A Foundations of Crystallography, 2004
Acta Crystallographica Section A Foundations of Crystallography, 2004
Acta Crystallographica Section A Foundations of Crystallography, 2004
Croatica Chemica Acta, 2009
Molecular recognition is a key process in non-covalent interactions, which determines, among othe... more Molecular recognition is a key process in non-covalent interactions, which determines, among others, host-guest complexation, drug action and protein-protein interaction. A simple and attractive formulation is the lock-and-key analogy defining the host as a lock accommodating the guest as a key. We stress three major aspects of molecular recognition, determining both complementarity between host and guest and similarity within a group of guest molecules. These aspects are: steric, i.e. maximization of close contacts, electrostatic, i.e. maximization of electrostatic attraction between host and guest, as well as hydrophobic, i.e. avoiding hydrophobic hydration, which can be reached by the maximization of apolar contacts between interacting molecules. Some examples are presented from our laboratory: the complexes of acylaminoacyl peptidase with small peptides, the effect of heparin binding on inhibitory potency of C1inhibitor as well as small-molecule ligand binding to prolyl oligopeptidase and calmodulin.
Theoretical Chemistry Accounts, 2007
Phosphate ester hydrolysis is a key step in several enzymatic processes, which follow either a di... more Phosphate ester hydrolysis is a key step in several enzymatic processes, which follow either a dissociative or an associative mechanism. While in the aqueous phase both pathways are favoured to about the same extent, the associative mechanism is relatively rarely observed. In this paper we report on quantum mechanical calculations for three enzymes HIV integrase, β-phosphoglucomutase and dUTPase, and try to find an explanation for the preference of the associative mechanism in a given enzyme. It is reasonable to suppose that the stabilisation of the pentacovalent, trigonal bipyramidal phosphorane moiety by formation of a covalent bond, one or more hydrogen bonds, or by coordination of a divalent metal cation with the equatorial oxygen atoms is the key factor. In all three enzymes studied one of the equatorial oxygen atoms is coordinated to a magnesium dication, while a second one is involved in a covalent bond. While in HIV integrase the third oxygen atom may only form a weak hydrogen bond with a solvent water molecule, in β-phosphoglucomutase this atom is stabilised by two strong hydrogen Contribution to the Fernando Bernardi Memorial Issue.
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Papers by Gábor Náray/Szabó