Linked Life Data

15206933

Source:http://linkedlifedata.com/resource/pubmed/id/15206933

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-6-21
pubmed:abstractText
UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), catalyzes the first step in the biosynthesis of peptidoglycan, involving the transfer of the intact enolpyruvyl moiety from phosphoenolpyruvate to the 3'-hydroxyl group of UDP-N-acetylglucosamine (UDPNAG). The enzyme is irreversibly inhibited by the antibiotic fosfomycin. The inactivation is caused by alkylation of a highly conserved cysteine residue (C115) that participates in the binding of phosphoenolpyruvate. The three-dimensional structure of the enzyme suggests that two residues may play a decisive role in fosfomycin binding: K22 and R120. To investigate the role of these residues, we have generated the K22V, K22E, K22R and R120K single mutant proteins as well as the K22V/R120K and K22V/R120V double mutant proteins. We demonstrated that the K22R mutant protein behaves similarly to wild-type enzyme, whereas the K22E mutant protein failed to form the covalent adduct. On the other hand, the K22V mutant protein requires the presence of UDPNAG for the formation of the adduct indicating that UDPNAG plays a crucial role in the organization of productive interactions in the active site. This model receives strong support from heat capacity changes observed for the K22V/R120K and R120K mutant proteins: in both mutant proteins, the heat capacity changes are markedly reduced indicating that their ability to form a closed protein conformation is impeded due to the R120K exchange.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2682-90
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Role of K22 and R120 in the covalent binding of the antibiotic fosfomycin and the substrate-induced conformational change in UDP-N-acetylglucosamine enolpyruvyl transferase.
pubmed:affiliation
Eidgenössische Technische Hochschule Zürich, Institute of Plant Sciences, Department of Agricultural and Food Sciences and Department of Biology, Zürich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't