Linked Life Data

18161993

Source:http://linkedlifedata.com/resource/pubmed/id/18161993

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-16
pubmed:abstractText
Protein-water interactions have long been recognized as a major determinant of chain folding, conformational stability, binding specificity and catalysis. However, the detailed effects of water on stabilizing protein-protein interactions remain elusive. A way to test experimentally the contribution of water-mediated interactions is by applying double mutant cycle analysis on pairs of residues that do not form direct interactions, but are bridged by water. Seven such interactions within the interface between TEM1 and BLIP proteins were evaluated. No significant interaction free energy was found between either of them. Water can bridge interactions, but also stabilize the structure of the monomer. To distinguish between these, we performed a bioinformatic analysis using AQUAPROT (http://bioinfo.weizmann.ac.il/aquaprot) to determine the degree of water conservation between the bound and unbound states. 29 structures of twelve complexes and 20 related monomers were analyzed. Of the 262 water molecules located within the interfaces, 145 were conserved between the unbound and bound structures. Strikingly, all 50 buried or partially buried waters in the monomer structures were conserved at the same location in the bound structures. Thus, buried waters have an important role in stabilizing the monomer fold rather than contributing to protein-protein binding, and are not replaced by residues from the incoming protein. Taking together the experimental and bioinformatics evidence suggests that exposed waters within the interface may be good sites for protein engineering, while buried or mostly buried waters should be left unchanged.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1051-60
pubmed:dateRevised
2008-8-22
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
On the contribution of water-mediated interactions to protein-complex stability.
pubmed:affiliation
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't