1eq2
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(New page: 200px<br /><applet load="1eq2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eq2, resolution 2.0Å" /> '''THE CRYSTAL STRUCTURE...)
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Revision as of 12:06, 20 November 2007
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THE CRYSTAL STRUCTURE OF ADP-L-GLYCERO-D-MANNOHEPTOSE 6-EPIMERASE
Overview
BACKGROUND: ADP-L-glycero--mannoheptose 6-epimerase (AGME) is required for, lipopolysaccharide (LPS) biosynthesis in most genera of pathogenic and, non-pathogenic Gram-negative bacteria. It catalyzes the interconversion of, ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose, a precursor, of the seven-carbon sugar L-glycero-mannoheptose (heptose). Heptose is an, obligatory component of the LPS core domain; its absence results in a, truncated LPS structure resulting in susceptibility to hydrophobic, antibiotics. Heptose is not found in mammalian cells, thus its, biosynthetic pathway in bacteria presents a unique target for the design, of novel antimicrobial agents. RESULTS: The structure of AGME, in complex, with NADP and the catalytic inhibitor ADP-glucose, has been determined at, 2.0 A resolution by multiwavelength anomalous diffraction (MAD) phasing, methods. AGME is a homopentameric enzyme, which crystallizes with two, pentamers in the asymmetric unit. The location of 70 crystallographically, independent selenium sites was a key step in the structure determination, process. Each monomer comprises two domains: a large N-terminal domain, consisting of a modified seven-stranded Rossmann fold that is associated, with NADP binding; and a smaller alpha/beta C-terminal domain involved in, substrate binding. CONCLUSIONS: The first structure of an LPS core, biosynthetic enzyme leads to an understanding of the mechanism of the, conversion between ADP-D-glycero--mannoheptose and, ADP-L-glycero-D-mannoheptose. On the basis of its high structural, similarity to UDP-galactose epimerase and the three-dimensional positions, of the conserved residues Ser116, Tyr140 and Lys144, AGME was classified, as a member of the short-chain dehydrogenase/reductase (SDR) superfamily., This study should prove useful in the design of mechanistic and, structure-based inhibitors of the AGME catalyzed reaction.
About this Structure
1EQ2 is a Single protein structure of sequence from Escherichia coli with NAP and ADQ as ligands. Active as ADP-glyceromanno-heptose 6-epimerase, with EC number 5.1.3.20 Full crystallographic information is available from OCA.
Reference
The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist., Deacon AM, Ni YS, Coleman WG Jr, Ealick SE, Structure. 2000 May 15;8(5):453-62. PMID:10896473
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