1EIX

STRUCTURE OF OROTIDINE 5'-MONOPHOSPHATE DECARBOXYLASE FROM E. COLI, CO-CRYSTALLISED WITH THE INHIBITOR BMP

Summary for 1EIX

• Entry DOI: 10.2210/pdb1eix/pdb
• Descriptor: OROTIDINE 5'-MONOPHOSPHATE DECARBOXYLASE, 1-(5'-PHOSPHO-BETA-D-RIBOFURANOSYL)BARBITURIC ACID (3 entities in total)
• Functional Keywords: alpha-beta-barrel, protein-inhibitor complex, homodimer, lyase
• Biological source: Escherichia coli
• Total number of polymer chains: 4
• Total formula weight: 106873.62

Authors

Harris, P.,Poulsen, J.C.N.,Jensen, K.F.,Larsen, S. (deposition date: 2000-02-29, release date: 2000-03-15, Last modification date: 2024-03-13)

Primary citation

Harris, P.,Poulsen, J.C.N.,Jensen, K.F.,Larsen, S.
Structural basis for the catalytic mechanism of a proficient enzyme: orotidine 5'-monophosphate decarboxylase.
Biochemistry, 39:4217-4224, 2000

PubMed Abstract: Orotidine 5'-monophosphate decarboxylase (ODCase) catalyzes the decarboxylation of orotidine 5'-monophosphate, the last step in the de novo synthesis of uridine 5'-monophosphate. ODCase is a very proficient enzyme [Radzicka, A., and Wolfenden, R. (1995) Science 267, 90-93], enhancing the reaction rate by a factor of 10(17). This proficiency has been enigmatic, since it is achieved without metal ions or cofactors. Here we present a 2.5 A resolution structure of ODCase complexed with the inhibitor 1-(5'-phospho-beta-D-ribofuranosyl)barbituric acid. It shows a closely packed dimer composed of two alpha/beta-barrels with two shared active sites. The orientation of the orotate moiety of the substrate is unambiguously deduced from the structure, and previously proposed catalytic mechanisms involving protonation of O2 or O4 can be ruled out. The proximity of the OMP carboxylate group with Asp71 appears to be instrumental for the decarboxylation of OMP, either through charge repulsion or through the formation of a very short O.H.O hydrogen bond between the two carboxylate groups.

PubMed: 10757968
DOI: 10.1021/bi992952r

Experimental method

X-RAY DIFFRACTION (2.5 Å)