3O1N

1.03 Angstrom Crystal Structure of Q236A Mutant Type I Dehydroquinate Dehydratase (aroD) from Salmonella typhimurium

Summary for 3O1N

• Entry DOI: 10.2210/pdb3o1n/pdb
• Related: 3L2I 3LB0 3M7W 3NNT
• Descriptor: 3-dehydroquinate dehydratase, CHLORIDE ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: structural genomics, center for structural genomics of infectious diseases, csgid, tim barrel, dehydratase, lyase
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium
• Total number of polymer chains: 2
• Total formula weight: 60221.19

Authors

Light, S.H.,Minasov, G.,Shuvalova, L.,Papazisi, L.,Anderson, W.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2010-07-21, release date: 2010-08-11, Last modification date: 2023-09-06)

Primary citation

Light, S.H.,Minasov, G.,Shuvalova, L.,Peterson, S.N.,Caffrey, M.,Anderson, W.F.,Lavie, A.
A conserved surface loop in type I dehydroquinate dehydratases positions an active site arginine and functions in substrate binding.
Biochemistry, 50:2357-2363, 2011

PubMed 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.

PubMed: 21291284
DOI: 10.1021/bi102020s

Experimental method

X-RAY DIFFRACTION (1.03 Å)