Source:http://linkedlifedata.com/resource/pubmed/id/11124906
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2001-1-22
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Magnesium,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleotidyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/UDPacetylglucosamine...,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine Diphosphate...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-2836
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2001 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
305
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
279-89
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pubmed:dateRevised |
2006-11-15
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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
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pubmed:year |
2001
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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.
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pubmed:affiliation |
Pharmaceutical Research Chemical Technologies, F. Hoffmann-La Roche Ltd., Basle, 4070, Switzerland. dirk.kostrewa@psi.ch
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pubmed:publicationType |
Journal Article
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