3DDN

Crystal structure of hydroxypyruvic acid phosphate bound D-3-phosphoglycerate dehydrogenase in mycobacterium tuberculosis

3DDN の概要

• エントリーDOI: 10.2210/pdb3ddn/pdb
• 関連するPDBエントリー: 1YGY 3DC2
• 分子名称: D-3-phosphoglycerate dehydrogenase, L(+)-TARTARIC ACID, 2-oxo-3-(phosphonooxy)propanoic acid, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, phosphoglycerate dehydrogenase, serine biosynthesis, amino-acid biosynthesis, nad
• 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: 109782.03

構造登録者

Dey, S.,Sacchettini, J.C. (登録日: 2008-06-05, 公開日: 2008-07-22, 最終更新日: 2024-10-30)

主引用文献

Dey, S.,Burton, R.L.,Grant, G.A.,Sacchettini, J.C.
Structural analysis of substrate and effector binding in Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase
Biochemistry, 47:8271-8282, 2008

PubMed Abstract: The crystal structure of Mycobacterium tuberculosis d-3-phosphoglycerate dehydrogenase has been solved with bound effector, l-serine, and substrate, hydroxypyruvic acid phosphate, at resolutions of 2.7 and 2.4 A, respectively. The subunits display the same extreme asymmetry as seen in the apo-structure and provide insight into the mode of serine binding and closure of the active site. Mutagenesis studies confirm the identity of the main residues involved in serine binding and suggest that the poly glycine stretch in the loop that contains the locus for the 160 degrees rotation that leads to subunit asymmetry may have a larger role in folding than in catalysis. The lack of electron density for the cofactor, NADH, in any of the crystals examined led us to study binding by stopped flow kinetic analysis. The kinetic data suggest that productive NADH binding, that would support catalytic turnover, is dependent on the presence of substrate. This observation, along with the binding of substrate in the active site, but in an unproductive conformation, suggests a possible mechanism where initial binding of substrate leads to enhanced interaction with cofactor accompanied by a rearrangement of catalytically critical residue side chains. Furthermore, comparison to the structure of a truncated form of human d-3-phosphoglycerate dehydrogenase with cofactor and a substrate analog, provides insight into the conformational changes that occur during catalysis.

PubMed: 18627175
DOI: 10.1021/bi800212b

実験手法

X-RAY DIFFRACTION (2.4 Å)