2I8U

GDP-mannose mannosyl hydrolase-calcium-GDP product complex

2I8U の概要

• エントリーDOI: 10.2210/pdb2i8u/pdb
• 関連するPDBエントリー: 2I8O 2I8P 2I8Q 2I8R 2I8S 2I8T
• 分子名称: GDP-mannose mannosyl hydrolase, CALCIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: nudix enzyme, lipopolysaccharide, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39656.02

構造登録者

Zou, Y.,Li, C.,Brunzelle, J.S.,Nair, S.K. (登録日: 2006-09-03, 公開日: 2007-06-19, 最終更新日: 2024-02-21)

主引用文献

Zou, Y.,Li, C.,Brunzelle, J.S.,Nair, S.K.
Molecular basis for substrate selectivity and specificity by an LPS biosynthetic enzyme
Biochemistry, 46:4294-4304, 2007

PubMed Abstract: 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.

PubMed: 17371001
DOI: 10.1021/bi061056u

実験手法

X-RAY DIFFRACTION (1.4 Å)