View source for 1eq2

[[Image:1eq2.gif|left|200px]]

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{{STRUCTURE_1eq2|  PDB=1eq2  |  SCENE=  }} 

'''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 [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EQ2 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:[http://www.ncbi.nlm.nih.gov/pubmed/10896473 10896473]
[[Category: ADP-glyceromanno-heptose 6-epimerase]]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Deacon, A M.]]
[[Category: Ealick, S E.]]
[[Category: Jr., W G.Coleman.]]
[[Category: Ni, Y S.]]
[[Category: C-terminal mixed alpha/beta domain]]
[[Category: N-terminal domain rossmann fold]]
[[Category: Short-chain dehydrogenase/reductase fold]]
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