A conserved surface loop in type i dehydroquinate dehydratases positions an active site arginine and functions in substrate binding

Samuel H. Light, George Minasov, Ludmilla A Shuvalova, Scott N. Peterson, Michael Caffrey, Wayne F Anderson, Arnon Lavie*

*Corresponding author for this work

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2357-2363
Number of pages7
JournalBiochemistry
Volume50
Issue number12
DOIs
StatePublished - Mar 29 2011

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'A conserved surface loop in type i dehydroquinate dehydratases positions an active site arginine and functions in substrate binding'. Together they form a unique fingerprint.

  • Cite this