Linked Life Data

11545592

Source:http://linkedlifedata.com/resource/pubmed/id/11545592

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-9-7
pubmed:databankReference
pubmed:abstractText
The enzyme CMP-Kdo synthetase (CKS) catalyzes the activation of the sugar Kdo (2-keto-3-deoxy-manno-octonic acid) by forming a monophosphate diester. CKS is a pharmaceutical target because CMP-Kdo is used in the biosynthesis of lipopolysaccharides that are vital for Gram-negative bacteria. We have refined the structure of the unligated capsule-specific CKS from Escherichia coli at 1.8 A resolution (1 A=0.1 nm) and we have established the structures of its complexes with the substrate CTP, with CDP and CMP as well as with the product analog CMP-NeuAc (CMP-sialate) by X-ray diffraction analyses at resolutions between 2.1 A and 2.5 A. The N-terminal domains of the dimeric enzyme bind CTP in a peculiar nucleotide-binding fold, whereas the C-terminal domains form the dimer interface. The observed binding geometries together with the amino acid variabilities during evolution and the locations of a putative Mg(2+) and of a very strongly bound water molecule suggest a pathway for the catalysis. The N-terminal domain shows sequence homology with the CMP-NeuAc synthetases. Moreover, the chain fold and the substrate-binding position of CKS resemble those of other enzymes processing nucleotide-sugars.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
312
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-55
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11545592-Amino Acid Sequence, pubmed-meshheading:11545592-Conserved Sequence, pubmed-meshheading:11545592-Crystallography, X-Ray, pubmed-meshheading:11545592-Cytidine Diphosphate, pubmed-meshheading:11545592-Cytidine Monophosphate, pubmed-meshheading:11545592-Cytidine Monophosphate N-Acetylneuraminic Acid, pubmed-meshheading:11545592-Cytidine Triphosphate, pubmed-meshheading:11545592-Dimerization, pubmed-meshheading:11545592-Escherichia coli, pubmed-meshheading:11545592-Models, Molecular, pubmed-meshheading:11545592-Molecular Sequence Data, pubmed-meshheading:11545592-N-Acylneuraminate Cytidylyltransferase, pubmed-meshheading:11545592-Nucleotidyltransferases, pubmed-meshheading:11545592-Protein Conformation, pubmed-meshheading:11545592-Protein Folding, pubmed-meshheading:11545592-Sequence Homology, Amino Acid
pubmed:year
2001
pubmed:articleTitle
The structure of CMP:2-keto-3-deoxy-manno-octonic acid synthetase and of its complexes with substrates and substrate analogs.
pubmed:affiliation
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Albertstr. 21, Freiburg im Breisgau, Germany, 79104.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't