A Conserved Surface Loop in Type I Dehydroquinate Dehydratases Positions an Active Site Arginine and Functions in Substrate Binding
详细信息 查看全文
- 作者：Samuel H. Light ; George Minasov ; Ludmilla Shuvalova ; Scott N. Peterson ; Michael Caffrey ; Wayne F. Anderson ; Arnon Lavie
- 刊名：Biochemistry
- 出版年：2011
- 出版时间：March 29, 2011
- 年：2011
- 卷：50
- 期：12
- 页码：2357-2363
- 全文大小：880K
- 年卷期：v.50,no.12(March 29, 2011)
- ISSN：1520-4995
文摘
Dehydroquinate dehydratase (DHQD) catalyzes the third step in the biosynthetic shikimate pathway. We present three crystal structures of the Salmonella enterica type I DHQD that address the functionality of a surface loop that is observed to close over the active site following substrate binding. Two wild-type structures with differing loop conformations and kinetic and structural studies of a mutant provide evidence of both direct and indirect mechanisms of involvement of the loop in substrate binding. In addition to allowing amino acid side chains to establish a direct interaction with the substrate, closure of the loop necessitates a conformational change of a key active site arginine, which in turn positions the substrate productively. The absence of DHQD in humans and its essentiality in many pathogenic bacteria make the enzyme a target for the development of nontoxic antimicrobials. The structures and ligand binding insights presented here may inform the design of novel type I DHQD inhibiting molecules.