2VOR

Crystal Structures of Mycobacterium tuberculosis Folylpolyglutamate Synthase Complexed with ADP and AMPPCP

2VOR の概要

• エントリーDOI: 10.2210/pdb2vor/pdb
• 関連するPDBエントリー: 2VOS
• 分子名称: FOLYLPOLYGLUTAMATE SYNTHASE PROTEIN FOLC, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, COBALT (II) ION, ... (5 entities in total)
• 機能のキーワード: ligase, peptidoglycan synthesis, cell division, folate metabolism, cell wall biogenesis/degradation
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51753.19

構造登録者

Young, P.G.,Baker, E.N.,Metcalf, P.,Smith, C.A. (登録日: 2008-02-19, 公開日: 2008-07-01, 最終更新日: 2024-05-01)

主引用文献

Young, P.G.,Smith, C.A.,Metcalf, P.,Baker, E.N.
Structures of Mycobacterium Tuberculosisfolylpolyglutamate Synthase Complexed with Adp and Amppcp.
Acta Crystallogr.,Sect.D, 64:745-, 2008

PubMed Abstract: Folate derivatives are essential vitamins for cell growth and replication, primarily because of their central role in reactions of one-carbon metabolism. Folates require polyglutamation to be efficiently retained within the cell and folate-dependent enzymes have a higher affinity for the polyglutamylated forms of this cofactor. Polyglutamylation is dependent on the enzyme folylpolyglutamate synthetase (FPGS), which catalyzes the sequential addition of several glutamates to folate. FPGS is essential for the growth and survival of important bacterial species, including Mycobacterium tuberculosis, and is a potential drug target. Here, the crystal structures of M. tuberculosis FPGS in complex with ADP and AMPPCP are reported at 2.0 and 2.3 angstroms resolution, respectively. The structures reveal a deeply buried nucleotide-binding site, as in the Escherichia coli and Lactobacillus casei FPGS structures, and a long extended groove for the binding of folate substrates. Differences from the E. coli and L. casei FPGS structures are seen in the binding of a key divalent cation, the carbamylation state of an essential lysine side chain and the adoption of an 'open' position by the active-site beta5-alpha6 loop. These changes point to coordinated events that are associated with dihydropteroate/folate binding and the catalysis of the new amide bond with an incoming glutamate residue.

PubMed: 18566510
DOI: 10.1107/S0907444908012262

実験手法

X-RAY DIFFRACTION (2.3 Å)