3LHV

Crystal structure of the mutant V182A.I199A.V201A of orotidine 5'-monophosphate decarboxylase from Methanobacterium thermoautotrophicum complexed with inhibitor BMP

Summary for 3LHV

• Entry DOI: 10.2210/pdb3lhv/pdb
• Related: 3LHT 3LHU 3LHW 3LHY 3LHZ 3LI0 3LI1
• Descriptor: Orotidine 5'-phosphate decarboxylase, 1-(5'-PHOSPHO-BETA-D-RIBOFURANOSYL)BARBITURIC ACID (3 entities in total)
• Functional Keywords: mutant v182a.i199a.v201a, 6-hydroxyuridine-5'-phosphate, decarboxylase, pyrimidine biosynthesis, lyase
• Biological source: Methanothermobacter thermautotrophicus
• Total number of polymer chains: 4
• Total formula weight: 100506.77

Authors

Fedorov, A.A.,Fedorov, E.V.,Wood, B.M.,Gerlt, J.A.,Almo, S.C. (deposition date: 2010-01-23, release date: 2010-06-16, Last modification date: 2023-09-06)

Primary citation

Wood, B.M.,Amyes, T.L.,Fedorov, A.A.,Fedorov, E.V.,Shabila, A.,Almo, S.C.,Richard, J.P.,Gerlt, J.A.
Conformational changes in orotidine 5'-monophosphate decarboxylase: "remote" residues that stabilize the active conformation.
Biochemistry, 49:3514-3516, 2010

PubMed Abstract: The structural factors responsible for the extraordinary rate enhancement ( approximately 10(17)) of the reaction catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) have not been defined. Catalysis requires a conformational change that closes an active site loop and "clamps" the orotate base proximal to hydrogen-bonded networks that destabilize the substrate and stabilize the intermediate. In the OMPDC from Methanobacter thermoautotrophicus, a "remote" structurally conserved cluster of hydrophobic residues that includes Val 182 in the active site loop is assembled in the closed, catalytically active conformation. Substitution of these residues with Ala decreases k(cat)/K(m) with a minimal effect on k(cat), providing evidence that the cluster stabilizes the closed conformation. The intrinsic binding energies of the 5'-phosphate group of orotidine 5'-monophosphate for the mutant enzymes are similar to that for the wild type, supporting this conclusion.

PubMed: 20369850
DOI: 10.1021/bi100443a

Experimental method

X-RAY DIFFRACTION (1.35 Å)