Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.03
Classification:LYASE
Release Date:2010-08-11
Deposition Date:2010-07-21
Revision Date:2011-07-13#2017-11-08
Molecular Weight:60221.19
Macromolecule Type:Protein
Residue Count:552
Atom Site Count:4102
DOI:10.2210/pdb3o1n/pdb
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.
Resolution:1.03
Classification:LYASE
Release Date:2010-08-11
Deposition Date:2010-07-21
Revision Date:2011-07-13#2017-11-08
Molecular Weight:60221.19
Macromolecule Type:Protein
Residue Count:552
Atom Site Count:4102
DOI:10.2210/pdb3o1n/pdb
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.
| Date made available | 2010 |
|---|---|
| Publisher | RCSB-PDB |