3GNC

Crystal structure of Glutaryl-COA dehydrogenase from Burkholderia Pseudomallei with fragment 6421

3GNC の概要

• エントリーDOI: 10.2210/pdb3gnc/pdb
• 関連するPDBエントリー: 3d6B
• 分子名称: Glutaryl-CoA dehydrogenase, SULFATE ION, 1-(1-methylethyl)-1H-benzimidazole-2-sulfonic acid, ... (5 entities in total)
• 機能のキーワード: oxidoreductase, structural genomics, seattle structural genomics center for infectious disease, ssgcid
• 由来する生物種: Burkholderia pseudomallei
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 175642.27

構造登録者

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2009-03-16, 公開日: 2009-07-07, 最終更新日: 2023-09-06)

主引用文献

Begley, D.W.,Davies, D.R.,Hartley, R.C.,Hewitt, S.N.,Rychel, A.L.,Myler, P.J.,Van Voorhis, W.C.,Staker, B.L.,Stewart, L.J.
Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening.
Acta Crystallogr.,Sect.F, 67:1060-1069, 2011

PubMed Abstract: Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.

PubMed: 21904051
DOI: 10.1107/S1744309111014436

実験手法

X-RAY DIFFRACTION (2.15 Å)