3OVQ

Crystal Structure of hRPE and D-Ribulose-5-Phospate Complex

3OVQ の概要

• エントリーDOI: 10.2210/pdb3ovq/pdb
• 関連するPDBエントリー: 3OVP 3OVR
• 分子名称: Ribulose-phosphate 3-epimerase, FE (II) ION, RIBULOSE-5-PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: d-ribulose-5-phosphate, isomerase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53691.15

構造登録者

Liang, W.G.,Ouyang, S.Y.,Shaw, N.,Joachimiak, A.,Zhang, R.G.,Liu, Z.J. (登録日: 2010-09-17, 公開日: 2011-03-09, 最終更新日: 2024-10-16)

主引用文献

Liang, W.G.,Ouyang, S.Y.,Shaw, N.,Joachimiak, A.,Zhang, R.G.,Liu, Z.J.
Conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate: new insights from structural and biochemical studies on human RPE
Faseb J., 25:497-504, 2011

PubMed Abstract: The pentose phosphate pathway (PPP) confers protection against oxidative stress by supplying NADPH necessary for the regeneration of glutathione, which detoxifies H(2)O(2) into H(2)O and O(2). RPE functions in the PPP, catalyzing the reversible conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate and is an important enzyme for cellular response against oxidative stress. Here, using structural, biochemical, and functional studies, we show that human D-ribulose 5-phosphate 3-epimerase (hRPE) uses Fe(2+) for catalysis. Structures of the binary complexes of hRPE with D-ribulose 5-phosphate and D-xylulose 5-phosphate provide the first detailed molecular insights into the binding mode of physiological ligands and reveal an octahedrally coordinated Fe(2+) ion buried deep inside the active site. Human RPE folds into a typical (β/α)(8) triosephosphate isomerase (TIM) barrel with a loop regulating access to the active site. Two aspartic acids are well positioned to carry out the proton transfers in an acid-base type of reaction mechanism. Interestingly, mutating Ser-10 to alanine almost abolished the enzymatic activity, while L12A and M72A mutations resulted in an almost 50% decrease in the activity. The binary complexes of hRPE reported here will aid in the design of small molecules for modulating the activity of the enzyme and altering flux through the PPP.

PubMed: 20923965
DOI: 10.1096/fj.10-171207

実験手法

X-RAY DIFFRACTION (1.999 Å)