Linked Life Data

11124906

Source:http://linkedlifedata.com/resource/pubmed/id/11124906

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-1-22
pubmed:databankReference
pubmed:abstractText
N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) is an essential bacterial enzyme with both an acetyltransferase and a uridyltransferase activity which have been mapped to the C-terminal and N-terminal domains, respectively. GlmU performs the last two steps in the synthesis of UDP-N-acetylglucosamine (UDP-GlcNAc), which is an essential precursor in both the peptidoglycan and the lipopolysaccharide metabolic pathways. GlmU is therefore an attractive target for potential antibiotics. Knowledge of its three-dimensional structure would provide a basis for rational drug design. We have determined the crystal structures of Streptococcus pneumoniae GlmU (SpGlmU) in apo form at 2.33 A resolution, and in complex with UDP-N-acetyl glucosamine and the essential co-factor Mg(2+) at 1.96 A resolution. The protein structure consists of an N-terminal domain with an alpha/beta-fold, containing the uridyltransferase active site, and a C-terminal domain with a long left-handed beta-sheet helix (LbetaH) domain. An insertion loop containing the highly conserved sequence motif Asn-Tyr-Asp-Gly protrudes from the left-handed beta-sheet helix domain. In the crystal, S. pneumoniae GlmU forms exact trimers, mainly through contacts between left-handed beta-sheet helix domains. UDP-N-acetylglucosamine and Mg(2+) are bound at the uridyltransferase active site, which is in a closed form. We propose a uridyltransferase mechanism in which the activation energy of the double negatively charged phosphorane transition state is lowered by charge compensation of Mg(2+) and the side-chain of Lys22.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
305
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
279-89
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11124906-Amino Acid Motifs, pubmed-meshheading:11124906-Amino Acid Sequence, pubmed-meshheading:11124906-Apoenzymes, pubmed-meshheading:11124906-Binding Sites, pubmed-meshheading:11124906-Conserved Sequence, pubmed-meshheading:11124906-Crystallography, X-Ray, pubmed-meshheading:11124906-Escherichia coli, pubmed-meshheading:11124906-Hydrogen Bonding, pubmed-meshheading:11124906-Magnesium, pubmed-meshheading:11124906-Models, Molecular, pubmed-meshheading:11124906-Nucleotidyltransferases, pubmed-meshheading:11124906-Protein Structure, Secondary, pubmed-meshheading:11124906-Protein Structure, Tertiary, pubmed-meshheading:11124906-Sequence Deletion, pubmed-meshheading:11124906-Streptococcus pneumoniae, pubmed-meshheading:11124906-Structure-Activity Relationship, pubmed-meshheading:11124906-Uridine Diphosphate N-Acetylglucosamine
pubmed:year
2001
pubmed:articleTitle
Crystal structures of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyltransferase, GlmU, in apo form at 2.33 A resolution and in complex with UDP-N-acetylglucosamine and Mg(2+) at 1.96 A resolution.
pubmed:affiliation
Pharmaceutical Research Chemical Technologies, F. Hoffmann-La Roche Ltd., Basle, 4070, Switzerland. dirk.kostrewa@psi.ch
pubmed:publicationType
Journal Article