The role of glu73 of barnase in catalysis and the binding of barstar

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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“…This leads to enthalpy/entropy compensation that results in small changes in nG values [39]. [38,41].…”

Section: Thermodynamics and Kinetics Of Protein-protein Interactionsmentioning

confidence: 99%

Protein‐protein interactions as a target for drugs in proteomics

et al. 2003

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“…The bovine pancreatic trypsin inhibitor ͑BPTI͒-trypsin system where the crucial P 1 residue had been mutated to various residues, and the binding constants and mutated protein complex structures have been extensively documented. 32 The other two systems are well studied barnase-barstar complex 33 and the Streptomyces griseus proteinase B ͑SGPB͒-turkey ovomucoid third domain complex ͑OMTKY3͒.…”

Section: E Preparation Of Protein Complex Structuresmentioning

confidence: 99%

“…As comparisons, the experimental data set from Schreiber et al 33 for barnase-barstar is used to correlate with our calculations. In Fig.…”

Section: B Binding Energy Calculations Of Barnase-barstar Complexesmentioning

confidence: 99%

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Calculations of the binding affinities of protein-protein complexes with the fast multipole method

Kim

Song

2010

The Journal of Chemical Physics

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In this paper, we used a coarse-grained model at the residue level to calculate the binding free energies of three protein-protein complexes. General formulations to calculate the electrostatic binding free energy and the van der Waals free energy are presented by solving linearized Poisson-Boltzmann equations using the boundary element method in combination with the fast multipole method. The residue level model with the fast multipole method allows us to efficiently investigate how the mutations on the active site of the proteinprotein interface affect the changes in binding affinities of protein complexes. Good correlations between the calculated results and the experimental ones indicate that our model can capture the dominant contributions to the protein-protein interactions. At the same time, additional effects on protein binding due to atomic details are also discussed in the context of the limitations of such a coarse-grained model.

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“…Finally diffractionquality crystals of Baba with both barstar cysteine residues, Cys40 and Cys82, mutated to alanines were used and the structure independently determined at 2.6,~ and 2.0 A resolution . Subsequent studies were oriented towards understanding the role of individual residues in the barnase-barstar interface by protein engineering (Jones et al, 1993;Schreiber & Fersht, 1993, 1995Schreiber et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Recognition of RNase Sa by the Inhibitor Barstar: Structure of the Complex at 1.7 Å Resolution

Ševčı́k

Urbanikova

Dauter

et al. 1998

Acta Crystallogr D Biol Crystallogr

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The 1.7 .~ resolution structure of RNase Sa complexed with the polypeptide inhibitor barstar is reported here. The crystals are in the hexagonal space group~ P65 with unit-cell dimensions a = b = 56.9, c = 135.8 A and the asymmetric unit contains one molecule of the complex. RNase Sa is an extracellular microbial ribonuclease produced by Streptomyces aureofaciens. Barstar is the natural inhibitor of barnase, the ribonuclease of Bacillus amyloliquefaciens. It inhibits RNase Sa and barnase in a similar manner by steric blocking of the active site. The structure of RNase Sa is very similar to that observed in crystals of the native enzyme and its complexes with nucleotides. Barstar retains the structure found in its complex with barnase. The accessible surface area of protein buried in the complex is about 300 ~2 smaller and there are fewer hydrogen bonds in the enzymeinhibitor interface in RNase Sa-barstar than in barnasebarstar, providing an explanation of the reduced binding affinity in the former. Previous studies of barstar complexes have used mutants of the inhibitor and this is the first structure which includes wild-type barstar.

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The role of glu73 of barnase in catalysis and the binding of barstar

Cited by 46 publications

References 39 publications

Protein‐protein interactions as a target for drugs in proteomics

Protein‐protein interactions as a target for drugs in proteomics

Calculations of the binding affinities of protein-protein complexes with the fast multipole method

Recognition of RNase Sa by the Inhibitor Barstar: Structure of the Complex at 1.7 Å Resolution

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