PMID- 10827167 OWN - NLM STAT- MEDLINE DCOM- 20000914 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 275 IP - 32 DP - 2000 Aug 11 TI - Crystal structure of dTDP-4-keto-6-deoxy-D-hexulose 3,5-epimerase from Methanobacterium thermoautotrophicum complexed with dTDP. PG - 24608-12 AB - Deoxythymidine diphosphate (dTDP)-4-keto-6-deoxy-d-hexulose 3, 5-epimerase (RmlC) is involved in the biosynthesis of dTDP-l-rhamnose, which is an essential component of the bacterial cell wall. The crystal structure of RmlC from Methanobacterium thermoautotrophicum was determined in the presence and absence of dTDP, a substrate analogue. RmlC is a homodimer comprising a central jelly roll motif, which extends in two directions into longer beta-sheets. Binding of dTDP is stabilized by ionic interactions to the phosphate group and by a combination of ionic and hydrophobic interactions with the base. The active site, which is located in the center of the jelly roll, is formed by residues that are conserved in all known RmlC sequence homologues. The conservation of the active site residues suggests that the mechanism of action is also conserved and that the RmlC structure may be useful in guiding the design of antibacterial drugs. FAU - Christendat, D AU - Christendat D AD - Division of Molecular and Structural Biology, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada. FAU - Saridakis, V AU - Saridakis V FAU - Dharamsi, A AU - Dharamsi A FAU - Bochkarev, A AU - Bochkarev A FAU - Pai, E F AU - Pai EF FAU - Arrowsmith, C H AU - Arrowsmith CH FAU - Edwards, A M AU - Edwards AM LA - eng SI - PDB/1EP0 SI - PDB/1EPZ GR - RR07707/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Macromolecular Substances) RN - 0 (Recombinant Proteins) RN - 0 (Thymine Nucleotides) RN - 491-97-4 (thymidine 5'-diphosphate) RN - EC 5.1.3.- (Carbohydrate Epimerases) RN - EC 5.1.3.13 (dTDP-4-ketorhamnose 3,5-epimerase) SB - IM MH - Amino Acid Sequence MH - Binding Sites MH - Carbohydrate Epimerases/*chemistry/genetics/*metabolism MH - Crystallography, X-Ray MH - Dimerization MH - Macromolecular Substances MH - Methanobacterium/*enzymology/genetics MH - Models, Molecular MH - Molecular Sequence Data MH - Protein Structure, Secondary MH - Recombinant Proteins/chemistry/metabolism MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - Thymine Nucleotides/chemistry/*metabolism EDAT- 2000/05/29 09:00 MHDA- 2000/09/19 11:01 CRDT- 2000/05/29 09:00 PHST- 2000/05/29 09:00 [pubmed] PHST- 2000/09/19 11:01 [medline] PHST- 2000/05/29 09:00 [entrez] AID - S0021-9258(19)62214-3 [pii] AID - 10.1074/jbc.C000238200 [doi] PST - ppublish SO - J Biol Chem. 2000 Aug 11;275(32):24608-12. doi: 10.1074/jbc.C000238200.