1XGE

Dihydroorotase from Escherichia coli: Loop Movement and Cooperativity between subunits

Summary for 1XGE

• Entry DOI: 10.2210/pdb1xge/pdb
• Descriptor: Dihydroorotase, ZINC ION, (4S)-2,6-DIOXOHEXAHYDROPYRIMIDINE-4-CARBOXYLIC ACID, ... (5 entities in total)
• Functional Keywords: tim barrel, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 78138.04

Authors

Lee, M.,Chan, C.W.,Guss, J.M.,Christopherson, R.I.,Maher, M.J. (deposition date: 2004-09-17, release date: 2005-04-26, Last modification date: 2023-11-15)

Primary citation

Lee, M.,Chan, C.W.,Guss, J.M.,Christopherson, R.I.,Maher, M.J.
Dihydroorotase from Escherichia coli: Loop Movement and Cooperativity between Subunits
J.Mol.Biol., 348:523-533, 2005

PubMed Abstract: Escherichia coli dihydroorotase has been crystallized in the presence of the product, L-dihydroorotate (L-DHO), and the structure refined at 1.9A resolution. The structure confirms that previously reported (PDB entry 1J79), crystallized in the presence of the substrate N-carbamyl-D,L-aspartate (D, L-CA-asp), which had a dimer in the asymmetric unit, with one subunit having the substrate, L-CA-asp bound at the active site and the other having L-DHO. Importantly, no explanation for the unusual structure was given. Our results now show that a loop comprised of residues 105-115 has different conformations in the two subunits. In the case of the L-CA-asp-bound subunit, this loop reaches in toward the active site and makes hydrogen-bonding contact with the bound substrate molecule. For the L-DHO-bound subunit, the loop faces in the opposite direction and forms part of the surface of the protein. Analysis of the kinetics for conversion of L-DHO to L-CA-asp at low concentrations of L-DHO shows positive cooperativity with a Hill coefficient n=1.57(+/-0.13). Communication between subunits in the dimer may occur via cooperative conformational changes of the side-chains of a tripeptide from each subunit: Arg256-His257-Arg258, near the subunit interface.

PubMed: 15826651
DOI: 10.1016/j.jmb.2005.01.067

Experimental method

X-RAY DIFFRACTION (1.9 Å)