Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase. / Harris, Pernille Hanne; Poulsen, Jens-Christian Navarro; Jensen, Kaj Frank; Larsen, Sine.
I: Biochemistry, Bind 39, Nr. 15, 2000, s. 4217-4224.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase
AU - Harris, Pernille Hanne
AU - Poulsen, Jens-Christian Navarro
AU - Jensen, Kaj Frank
AU - Larsen, Sine
PY - 2000
Y1 - 2000
N2 - 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 1017. This proficiency has been enigmatic, since it is achieved without metal ions or cofactors. Here we present a 2.5 Å resolution structure of ODCase complexed with the inhibitor 1-(5‘-phospho-ß-d-ribofuranosyl)barbituric acid. It shows a closely packed dimer composed of two a/ß-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.
AB - 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 1017. This proficiency has been enigmatic, since it is achieved without metal ions or cofactors. Here we present a 2.5 Å resolution structure of ODCase complexed with the inhibitor 1-(5‘-phospho-ß-d-ribofuranosyl)barbituric acid. It shows a closely packed dimer composed of two a/ß-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.
U2 - 10.1021/bi992952r
DO - 10.1021/bi992952r
M3 - Journal article
VL - 39
SP - 4217
EP - 4224
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 15
ER -
ID: 150368