PDBsum entry 3v1p

Lyase/lyase inhibitor

PDB id: 3v1p

Contents

Protein chains

220 a.a.

Ligands

BMP ×2

SO4 ×2

Waters ×454

PDB id:

3v1p

Name:

Lyase/lyase inhibitor

Title:

Crystal structure of the mutant q185a of orotidine 5'-monophosphate decarboxylase from methanobacterium thermoautotrophicum complexed with the inhibitor bmp

Structure:

Orotidine 5'-phosphate decarboxylase. Chain: a, b. Synonym: omp decarboxylase, ompdcase, ompdecase. Engineered: yes. Mutation: yes

Source:

Methanothermobacter thermautotrophicus. Organism_taxid: 187420. Strain: delta h. Gene: pyrf, mth_129. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.37Å R-factor: 0.166 R-free: 0.178

Authors:

A.A.Fedorov,E.V.Fedorov,B.Desai,J.A.Gerlt,S.C.Almo

Key ref:

B.J.Desai et al. (2012). Conformational changes in orotidine 5'-monophosphate decarboxylase: a structure-based explanation for how the 5'-phosphate group activates the enzyme. Biochemistry, 51, 8665-8678. PubMed id: 23030629

Date:

09-Dec-11 Release date: 21-Nov-12

Protein chains

O26232  (PYRF_METTH) -  Orotidine 5'-phosphate decarboxylase from Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H)

Seq: 228 a.a.

Struc: 220 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.4.1.1.23 - orotidine-5'-phosphate decarboxylase.
• Pathway: Pyrimidine Biosynthesis
• Reaction: orotidine 5'-phosphate + H⁺ = UMP + CO2

orotidine 5'-phosphate + H(+) = UMP + CO2 (Bound ligand (Het Group name = BMP) matches with 95.45% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Biochemistry 51:8665-8678 (2012)

PubMed id: 23030629

Conformational changes in orotidine 5'-monophosphate decarboxylase: a structure-based explanation for how the 5'-phosphate group activates the enzyme.

B.J.Desai, B.M.Wood, A.A.Fedorov, E.V.Fedorov, B.Goryanova, T.L.Amyes, J.P.Richard, S.C.Almo, J.A.Gerlt.

ABSTRACT

The binding of a ligand to orotidine 5'-monophosphate decarboxylase (OMPDC) is accompanied by a conformational change from an open, inactive conformation (E(o)) to a closed, active conformation (E(c)). As the substrate traverses the reaction coordinate to form the stabilized vinyl carbanion/carbene intermediate, interactions that destabilize the carboxylate group of the substrate and stabilize the intermediate (in the E(c)·S(⧧) complex) are enforced. Focusing on the OMPDC from Methanothermobacter thermautotrophicus, we find the "remote" 5'-phosphate group of the substrate activates the enzyme 2.4 × 10(8)-fold; the activation is equivalently described by an intrinsic binding energy (IBE) of 11.4 kcal/mol. We studied residues in the activation that (1) directly contact the 5'-phosphate group, (2) participate in a hydrophobic cluster near the base of the active site loop that sequesters the bound substrate from the solvent, and (3) form hydrogen bonding interactions across the interface between the "mobile" and "fixed" half-barrel domains of the (β/α)(8)-barrel structure. Our data support a model in which the IBE provided by the 5'-phosphate group is used to allow interactions both near the N-terminus of the active site loop and across the domain interface that stabilize both the E(c)·S and E(c)·S(⧧) complexes relative to the E(o)·S complex. The conclusion that the IBE of the 5'-phosphate group provides stabilization to both the E(c)·S and E(c)·S(⧧) complexes, not just the E(c)·S(⧧) complex, is central to understanding the structural origins of enzymatic catalysis as well as the requirements for the de novo design of enzymes that catalyze novel reactions.