3M1Z

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

Summary for 3M1Z

• Entry DOI: 10.2210/pdb3m1z/pdb
• Related: 3LTP 3M41 3M43 3M44 3M47 3M5X 3M5Y 3M5Z
• Descriptor: Orotidine 5'-phosphate decarboxylase, 6-HYDROXYURIDINE-5'-PHOSPHATE (3 entities in total)
• Functional Keywords: orotidine 5'-monophosphate decarboxylase, lyase
• Biological source: Methanothermobacter thermautotrophicus str. Delta H
• Total number of polymer chains: 2
• Total formula weight: 50337.55

Authors

Fedorov, A.A.,Fedorov, E.V.,Wood, B.M.,Gerlt, J.A.,Almo, S.C. (deposition date: 2010-03-06, 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 (1.42 Å)