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| - | [[Image:2om2.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2om2| PDB=2om2 | SCENE= }} | | {{STRUCTURE_2om2| PDB=2om2 | SCENE= }} |
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| - | '''Crystal Structure Of Human G[alpha]i1 Bound To The Goloco Motif Of Rgs14'''
| + | ===Crystal Structure Of Human G[alpha]i1 Bound To The Goloco Motif Of Rgs14=== |
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| - | ==Overview==
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| - | The ability to manipulate protein binding affinities is important for the development of proteins as biosensors, industrial reagents, and therapeutics. We have developed a structure-based method to rationally predict single mutations at protein-protein interfaces that enhance binding affinities. The protocol is based on the premise that increasing buried hydrophobic surface area and/or reducing buried hydrophilic surface area will generally lead to enhanced affinity if large steric clashes are not introduced and buried polar groups are not left without a hydrogen bond partner. The procedure selects affinity enhancing point mutations at the protein-protein interface using three criteria: (1) the mutation must be from a polar amino acid to a non-polar amino acid or from a non-polar amino acid to a larger non-polar amino acid, (2) the free energy of binding as calculated with the Rosetta protein modeling program should be more favorable than the free energy of binding calculated for the wild-type complex and (3) the mutation should not be predicted to significantly destabilize the monomers. The performance of the computational protocol was experimentally tested on two separate protein complexes; Galpha(i1) from the heterotrimeric G-protein system bound to the RGS14 GoLoco motif, and the E2, UbcH7, bound to the E3, E6AP from the ubiquitin pathway. Twelve single-site mutations that were predicted to be stabilizing were synthesized and characterized in the laboratory. Nine of the 12 mutations successfully increased binding affinity with five of these increasing binding by over 1.0 kcal/mol. To further assess our approach we searched the literature for point mutations that pass our criteria and have experimentally determined binding affinities. Of the eight mutations identified, five were accurately predicted to increase binding affinity, further validating the method as a useful tool to increase protein-protein binding affinities. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17603074}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17603074 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17603074}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Arginine finger]] | | [[Category: Arginine finger]] |
| | [[Category: Rgs14 goloco]] | | [[Category: Rgs14 goloco]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:11:45 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:15:26 2008'' |
Revision as of 11:15, 28 July 2008
Template:STRUCTURE 2om2
Crystal Structure Of Human G[alpha]i1 Bound To The Goloco Motif Of Rgs14
Template:ABSTRACT PUBMED 17603074
About this Structure
2OM2 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure-based protocol for identifying mutations that enhance protein-protein binding affinities., Sammond DW, Eletr ZM, Purbeck C, Kimple RJ, Siderovski DP, Kuhlman B, J Mol Biol. 2007 Aug 31;371(5):1392-404. Epub 2007 Jun 8. PMID:17603074
Page seeded by OCA on Mon Jul 28 14:15:26 2008
