Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase

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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

Harris, PH, Poulsen, J-CN, Jensen, KF & Larsen, S 2000, 'Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase', Biochemistry, bind 39, nr. 15, s. 4217-4224. https://doi.org/10.1021/bi992952r

APA

Harris, P. H., Poulsen, J-C. N., Jensen, K. F., & Larsen, S. (2000). Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase. Biochemistry, 39(15), 4217-4224. https://doi.org/10.1021/bi992952r

Vancouver

Harris PH, Poulsen J-CN, Jensen KF, Larsen S. Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase. Biochemistry. 2000;39(15):4217-4224. https://doi.org/10.1021/bi992952r

Author

Harris, Pernille Hanne ; Poulsen, Jens-Christian Navarro ; Jensen, Kaj Frank ; Larsen, Sine. / Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase. I: Biochemistry. 2000 ; Bind 39, Nr. 15. s. 4217-4224.

Bibtex

@article{5b1103f074c611dbbee902004c4f4f50,
title = "Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase",
abstract = "Orotidine 5{\textquoteleft}-monophosphate decarboxylase (ODCase) catalyzes the decarboxylation of orotidine 5{\textquoteleft}-monophosphate, the last step in the de novo synthesis of uridine 5{\textquoteleft}-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 {\AA} resolution structure of ODCase complexed with the inhibitor 1-(5{\textquoteleft}-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.",
author = "Harris, {Pernille Hanne} and Poulsen, {Jens-Christian Navarro} and Jensen, {Kaj Frank} and Sine Larsen",
year = "2000",
doi = "10.1021/bi992952r",
language = "English",
volume = "39",
pages = "4217--4224",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "15",

}

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