1h7f
THE STRUCTURE OF CMP:2-KETO-3-DEOXY-MANNO-OCTONIC ACID SYNTHETASE AND OF ITS COMPLEXES WITH SUBSTRATES AND SUBSTRATE ANALOGUES, CMP COMPLEX
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OverviewOverview
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.
About this StructureAbout this Structure
1H7F is a Single protein structure of sequence from Escherichia coli with C5P as ligand. Active as 3-deoxy-manno-octulosonate cytidylyltransferase, with EC number 2.7.7.38 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
The structure of CMP:2-keto-3-deoxy-manno-octonic acid synthetase and of its complexes with substrates and substrate analogs., Jelakovic S, Schulz GE, J Mol Biol. 2001 Sep 7;312(1):143-55. PMID:11545592
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