Amino acid residue: is it structural or functional?

Golovanov, Alexander P.; Efremov, Roman G.; Jaravine, Victor; Vergoten, Gérard; Arseniev, Alexander S.

doi:10.1016/0014-5793(95)01212-w

Cited by 12 publications

(6 citation statements)

References 33 publications

(33 reference statements)

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“…Analysis of polarity properties of CX2 reveals that residues in the tips of loops I-III have unfavorable environments in water-positive values of E solv and MHP, negative values of the structure-sequence compatibility score (S). In well-folded proteins, residues with such characteristics tend to change their environment to the more favorable one in the result of intermolecular interactions (Golovanov et al, 1995). In fact, insertion of CX2 into the hydrophobic core or moderately polar interfacial region of membrane results in significant "improvement" of residues' environment in the loops.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Cardiotoxins with Membranes: A Molecular Modeling Study

Efremov

Volynsky

Nolde

et al. 2002

Biophysical Journal

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Incorporation of beta-sheet proteins into membrane is studied theoretically for the first time, and the results are validated by the direct experimental data. Using Monte Carlo simulations with implicit membrane, we explore spatial structure, energetics, polarity, and mode of insertion of two cardiotoxins with different membrane-destabilizing activity. Both proteins, classified as P- and S-type cardiotoxins, are found to retain the overall "three-finger" fold interacting with membrane core and lipid/water interface by the tips of the "fingers" (loops). The insertion critically depends upon the structure, hydrophobicity, and electrostatics of certain regions. The simulations reveal apparently distinct binding modes for S- and P-type cardiotoxins via the first loop or through all three loops, respectively. This rationalizes an earlier empirical classification of cardiotoxins into S- and P-type, and provides a basis for the analysis of experimental data on their membrane affinities. Accomplished with our previous simulations of membrane alpha-helices, the computational method may be used to study partitioning of proteins with diverse folds into lipid bilayers.

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Section: Discussionmentioning

confidence: 99%

Interaction of Cardiotoxins with Membranes: A Molecular Modeling Study

Efremov

Volynsky

Nolde

et al. 2002

Biophysical Journal

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“…These observations suggest that functional regions of the polypeptide chains evolved independently from the regions which are responsible for the structural stability, in order to avoid interference in the course of optimization. In fact, some authors classify conservative residues as structural or functional residues [7]. Furthermore, it is generally accepted that functionally important residues are mainly solvent‐accessible residues on the protein surface, while structurally important residues are likely part of the protein core [8].…”

Section: Introductionmentioning

confidence: 99%

Functionally and structurally relevant residues of enzymes: are they segregated or overlapping?

2004

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There is a delicate balance between stability and flexibility needed for enzyme function. To avoid undesirable alteration of the functional properties during the evolutionary optimization of the structural stability under certain circumstances, and vice versa, to avoid unwanted changes of stability during the optimization of the functional properties of proteins, common sense would suggest that parts of the protein structure responsible for stability and parts responsible for function developed and evolved separately. This study shows that nature did not follow this anthropomorphic logic: the set of residues involved in function and those involved in structural stabilization of enzymes are rather overlapping than segregated.

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“…This is probably the reason sometimes conservative residues are classified separately as residues conserved for structural or functional reasons. 30 Our survey on hundreds of unrelated proteins shows that nature does not follow this anthropomorphic logic.…”

Section: Relation Between Stabilization Center Elements and Secondary...mentioning

confidence: 96%

Noncovalent Cross-links in Context with Other Structural and Functional Elements of Proteins

Tüdös

Fiser

Simon

et al. 2004

J. Chem. Inf. Comput. Sci.

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Proteins are heteropolymers with evolutionary selected native sequences of residues. These native sequences code for unique and stable 3D structures indispensable for biochemical activity and for proteolysis resistance, the latter which guarantees an appropriate lifetime for the protein in the protease rich cellular environment. Cross-links between residues close in space but far in the primary structure are required to maintain the folded structure of proteins. Some of these cross-links are covalent, most frequently disulfide bonds, but the majority of the cross-links are sets of cooperative noncovalent long-range interactions. In this paper we focus on special clusters of noncovalent long-range interactions: the Stabilization Centers (SCs). The relation between the SCs and secondary structural elements as well as the relation between SCs and functionally important regions of proteins are presented to show a detailed picture of these clusters, which are believed to be primarily responsible for major aspects of protein stability.

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Amino acid residue: is it structural or functional?

Cited by 12 publications

References 33 publications

Interaction of Cardiotoxins with Membranes: A Molecular Modeling Study

Interaction of Cardiotoxins with Membranes: A Molecular Modeling Study

Functionally and structurally relevant residues of enzymes: are they segregated or overlapping?

Noncovalent Cross-links in Context with Other Structural and Functional Elements of Proteins

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