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| {{STRUCTURE_2i8u| PDB=2i8u | SCENE= }} | | {{STRUCTURE_2i8u| PDB=2i8u | SCENE= }} |
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| '''GDP-mannose mannosyl hydrolase-calcium-GDP product complex'''
| | ===GDP-mannose mannosyl hydrolase-calcium-GDP product complex=== |
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| ==Overview==
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| Diversity in the polysaccharide component of lipopolysaccharide (LPS) contributes to the persistence and pathogenesis of Gram-negative bacteria. The Nudix hydrolase GDP-mannose mannosyl hydrolase (Gmm) contributes to this diversity by regulating the concentration of mannose in LPS biosynthetic pathways. Here, we present seven high-resolution crystal structures of Gmm from the enteropathogenic E. coli strain O128: the structure of the apo enzyme, the cocrystal structure of Gmm bound to the product Mg2+-GDP, two cocrystal structures of precatalytic and turnover complexes of Gmm-Ca2+-GDP-alpha-d-mannose, and three cocrystal structures of an inactive mutant (His-124 --> Leu) Gmm bound to substrates GDP-alpha-d-mannose, GDP-alpha-d-glucose, and GDP-beta-l-fucose. These crystal structures help explain the molecular basis for substrate specificity and promiscuity and provide a structural framework for reconciling previously determined kinetic parameters. Unexpectedly, these structures reveal concerted changes in the enzyme structure that result in the formation of a catalytically competent active site only in the presence of the substrate/product. These structural views of the enzyme may provide a rationale for the design of inhibitors that target the biosynthesis of LPS by pathogenic bacteria.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17371001}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17371001 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17371001}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Lipopolysaccharide]] | | [[Category: Lipopolysaccharide]] |
| [[Category: Nudix enzyme]] | | [[Category: Nudix enzyme]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:12:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:35:27 2008'' |
