1LH0

Crystal Structure of Salmonella typhimurium OMP Synthase in Complex with MGPRPP and Orotate

1LH0 の概要

• エントリーDOI: 10.2210/pdb1lh0/pdb
• 関連するPDBエントリー: 1I2I
• 分子名称: OMP synthase, OROTIC ACID, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: loop closure, monomer closure, orotate phosphoribosyltransferase, transferase
• 由来する生物種: Salmonella typhimurium
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47910.51

構造登録者

Fedorov, A.A.,Panneerselvam, K.,Shi, W.,Grubmeyer, C.,Almo, S.C. (登録日: 2002-04-16, 公開日: 2002-05-08, 最終更新日: 2023-08-16)

主引用文献

Grubmeyer, C.,Hansen, M.R.,Fedorov, A.A.,Almo, S.C.
Structure of Salmonella typhimurium OMP Synthase in a Complete Substrate Complex.
Biochemistry, 51:4397-4405, 2012

PubMed Abstract: Dimeric Salmonella typhimurium orotate phosphoribosyltransferase (OMP synthase, EC 2.4.2.10), a key enzyme in de novo pyrimidine nucleotide synthesis, has been cocrystallized in a complete substrate E·MgPRPP·orotate complex and the structure determined to 2.2 Å resolution. This structure resembles that of Saccharomyces cerevisiae OMP synthase in showing a dramatic and asymmetric reorganization around the active site-bound ligands but shares the same basic topology previously observed in complexes of OMP synthase from S. typhimurium and Escherichia coli. The catalytic loop (residues 99-109) contributed by subunit A is reorganized to close the active site situated in subunit B and to sequester it from solvent. Furthermore, the overall structure of subunit B is more compact, because of movements of the amino-terminal hood and elements of the core domain. The catalytic loop of subunit B remains open and disordered, and subunit A retains the more relaxed conformation observed in loop-open S. typhimurium OMP synthase structures. A non-proline cis-peptide formed between Ala71 and Tyr72 is seen in both subunits. The loop-closed catalytic site of subunit B reveals that both the loop and the hood interact directly with the bound pyrophosphate group of PRPP. In contrast to dimagnesium hypoxanthine-guanine phosphoribosyltransferases, OMP synthase contains a single catalytic Mg(2+) in the closed active site. The remaining pyrophosphate charges of PRPP are neutralized by interactions with Arg99A, Lys100B, Lys103A, and His105A. The new structure confirms the importance of loop movement in catalysis by OMP synthase and identifies several additional movements that must be accomplished in each catalytic cycle. A catalytic mechanism based on enzymic and substrate-assisted stabilization of the previously documented oxocarbenium transition state structure is proposed.

PubMed: 22531064
DOI: 10.1021/bi300083p

実験手法

X-RAY DIFFRACTION (2 Å)