Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
A conserved surface loop in type I dehydroquinate dehydratases positions an active site arginine and functions in substrate binding.,Light SH, Minasov G, Shuvalova L, Peterson SN, Caffrey M, Anderson WF, Lavie A Biochemistry. 2011 Mar 29;50(12):2357-63. Epub 2011 Feb 21. PMID:21291284[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Light SH, Minasov G, Shuvalova L, Peterson SN, Caffrey M, Anderson WF, Lavie A. A conserved surface loop in type I dehydroquinate dehydratases positions an active site arginine and functions in substrate binding. Biochemistry. 2011 Mar 29;50(12):2357-63. Epub 2011 Feb 21. PMID:21291284 doi:10.1021/bi102020s
