2A8X

Crystal Structure of Lipoamide Dehydrogenase from Mycobacterium tuberculosis

2A8X の概要

• エントリーDOI: 10.2210/pdb2a8x/pdb
• 分子名称: Dihydrolipoyl dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• 機能のキーワード: lipoamide dehydrogenase; pyruvate dehydrogenase; alpha keto acid dehydrogenase, oxidoreductase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 100931.60

構造登録者

Rajashankar, K.R.,Bryk, R.,Kniewel, R.,Buglino, J.A.,Nathan, C.F.,Lima, C.D. (登録日: 2005-07-10, 公開日: 2005-08-16, 最終更新日: 2024-11-06)

主引用文献

Rajashankar, K.R.,Bryk, R.,Kniewel, R.,Buglino, J.A.,Nathan, C.F.,Lima, C.D.
Crystal structure and functional analysis of lipoamide dehydrogenase from Mycobacterium tuberculosis
J.Biol.Chem., 280:33977-33983, 2005

PubMed Abstract: We report the 2.4 A crystal structure for lipoamide dehydrogenase encoded by lpdC from Mycobacterium tuberculosis. Based on the Lpd structure and sequence alignment between bacterial and eukaryotic Lpd sequences, we generated single point mutations in Lpd and assayed the resulting proteins for their ability to catalyze lipoamide reduction/oxidation alone and in complex with other proteins that participate in pyruvate dehydrogenase and peroxidase activities. The results suggest that amino acid residues conserved in mycobacterial species but not conserved in eukaryotic Lpd family members modulate either or both activities and include Arg-93, His-98, Lys-103, and His-386. In addition, Arg-93 and His-386 are involved in forming both "open" and "closed" active site conformations, suggesting that these residues play a role in dynamically regulating Lpd function. Taken together, these data suggest protein surfaces that should be considered while developing strategies for inhibiting this enzyme.

PubMed: 16093239
DOI: 10.1074/jbc.M507466200

実験手法

X-RAY DIFFRACTION (2.4 Å)