Protein−Protein Interactions:  Interface Structure, Binding Thermodynamics, and Mutational Analysis

Stites, Wesley E.

doi:10.1021/cr960387h

Cited by 471 publications

(498 citation statements)

References 146 publications

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“…The average value of the contact surface of monomers is about 800 Å 2 [12,13]. Analysis of these surfaces revealed an increase in the number of arginine, histidine, asparagine, tryptophan, tyrosine and serine [13,14] and hydrophobic amino acid residues [12,15,16].…”

Section: Protein-protein Contacts: Structure Composition and Forcesmentioning

confidence: 99%

“…Analysis of protein contacts revealed that their interface surfaces are quite complementary to each other [12,13]. The degree of complementarity depends on the type of protein interaction.…”

Section: Protein-protein Contacts: Structure Composition and Forcesmentioning

confidence: 99%

“…The degree of complementarity depends on the type of protein interaction. Permanent complexes exhibit highest complementarity, whereas temporary complexes are characterized by lower complementarity and antigen-antibody complexes have the lowest complementarity [10,12,13]. Usually protein interfaces in protein complexes contain some cavities; their surfaces represent about 10% of total interface surfaces.…”

Section: Protein-protein Contacts: Structure Composition and Forcesmentioning

confidence: 99%

“…Conformational entropy is often subdivided into backbone and side chain contributions [39]. The backbone conformation entropy dominates in protein folding, and often it has very modest contribution to protein-protein interactions when backbone changes are minor [13]. The main contribution of the conformation entropy in the protein-protein interaction is usually the side chain component [39].…”

Section: Thermodynamics and Kinetics Of Protein-protein Interactionsmentioning

confidence: 99%

“…When the net entropy change is positive, the protein-protein interaction is entropy-driven reaction; in the opposite case, the enthalpy is the primary driving force of the interaction. The analysis of 69 complexes showed that in 31 cases the enthalpy is favorable but the entropy of association is unfavorable [13]. There are 18 cases where association is driven by entropy and enthapically opposed.…”

Section: Thermodynamics and Kinetics Of Protein-protein Interactionsmentioning

confidence: 99%

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Protein‐protein interactions as a target for drugs in proteomics

et al. 2003

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Protein-protein interactions play a central role in numerous processes in the cell and are one of the main fields of functional proteomics. This review highlights the methods of bioinformatics and functional proteomics of protein-protein interaction investigation. The structures and properties of contact surfaces, forces involved in protein-protein interactions, kinetic and thermodynamic parameters of these reactions were considered. The properties of protein contact surfaces depend on their functions. The contact surfaces of permanent complexes resemble domain contacts or the protein core and it is reasonable to consider such complex formation as a continuation of protein folding. Characteristics of contact surfaces of temporary protein complexes share some similarities with active sites of enzymes. The contact surfaces of the temporary protein complexes have unique structure and properties and they are more conservative in comparison with active site of enzymes. So they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations were undertaken to find or design small molecules that block protein dimerization or protein(peptide)-receptor interaction, or, on the contrary, to induce protein dimerization.

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Section: Protein-protein Contacts: Structure Composition and Forcesmentioning

confidence: 99%

Section: Protein-protein Contacts: Structure Composition and Forcesmentioning

confidence: 99%

Section: Protein-protein Contacts: Structure Composition and Forcesmentioning

confidence: 99%

Section: Thermodynamics and Kinetics Of Protein-protein Interactionsmentioning

confidence: 99%

Section: Thermodynamics and Kinetics Of Protein-protein Interactionsmentioning

confidence: 99%

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Protein‐protein interactions as a target for drugs in proteomics

et al. 2003

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Conservation of polar residues as hot spots at protein interfaces

et al. 2000

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A number of studies have addressed the question of which are the critical residues at protein-binding sites. These studies examined either a single or a few protein-protein interfaces. The most extensive study to date has been an analysis of alanine-scanning mutagenesis. However, although the total number of mutations was large, the number of protein interfaces was small, with some of the interfaces closely related. Here we show that although overall binding sites are hydrophobic, they are studded with specific, conserved polar residues at specific locations, possibly serving as energy "hot spots." Our results confirm and generalize the alanine-scanning data analysis, despite its limited size. Previously Trp, Arg, and Tyr were shown to constitute energetic hot spots. These were rationalized by their polar interactions and by their surrounding rings of hydrophobic residues. However, there was no compelling reason as to why specifically these residues were conserved. Here we show that other polar residues are similarly conserved. These conserved residues have been detected consistently in all interface families that we have examined. Our results are based on an extensive examination of residues which are in contact across protein interfaces. We utilize all clustered interface families with at least five members and with sequence similarity between the members in the range of 20-90%. There are 11 such clustered interface families, comprising a total of 97 crystal structures. Our three-dimensional superpositioning analysis of the occurrences of matched residues in each of the families identifies conserved residues at spatially similar environments. Additionally, in enzyme inhibitors, we observe that residues are more conserved at the interfaces than at other locations. On the other hand, antibody-protein interfaces have similar surface conservation as compared to their corresponding linear sequence alignment, consistent with the suggestion that evolution has optimized protein interfaces for function.

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Conservation of polar residues as hot spots at protein interfaces

Wolfson

et al. 2000

Proteins

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Protein−Protein Interactions: Interface Structure, Binding Thermodynamics, and Mutational Analysis

Cited by 471 publications

References 146 publications

Protein‐protein interactions as a target for drugs in proteomics

Protein‐protein interactions as a target for drugs in proteomics

Conservation of polar residues as hot spots at protein interfaces

Conservation of polar residues as hot spots at protein interfaces

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