1h7t: Difference between revisions

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.

1H7T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with SIA and C5P as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-deoxy-manno-octulosonate_cytidylyltransferase 3-deoxy-manno-octulosonate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.38 2.7.7.38] Structure known Active Sites: AC1 and AC2. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H7T OCA].  

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