1H7F

The structure of CMP:2-keto-3-deoxy-manno-octonic acid synthetase and of its complexes with substrates and substrate analogues, CMP complex

Summary for 1H7F

• Entry DOI: 10.2210/pdb1h7f/pdb
• Related: 1H6J 1H7E 1H7G 1H7H
• Descriptor: 3-DEOXY-MANNO-OCTULOSONATE CYTIDYLYLTRANSFERASE, CYTIDINE-5'-MONOPHOSPHATE (3 entities in total)
• Functional Keywords: nucleotidyltransferase, cmp-kdo synthetase, nucleoside monophosphate glycosides, lipopolysaccharide biosynthesis, sugar-activating enzymes
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 2
• Total formula weight: 54443.02

Authors

Jelakovic, S.,Schulz, G.E. (deposition date: 2001-07-06, release date: 2001-09-13, Last modification date: 2024-05-08)

Primary citation

Jelakovic, S.,Schulz, G.E.
The Structure of Cmp:2-Keto-3-Deoxy-Manno-Octonic Acid Synthetase and of its Complexes with Substrates and Substrate Analogs
J.Mol.Biol., 312:143-, 2001

PubMed Abstract: 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: 11545592
DOI: 10.1006/JMBI.2001.4948

Experimental method

X-RAY DIFFRACTION (2.12 Å)