2WWR

Crystal Structure of Human Glyoxylate Reductase Hydroxypyruvate Reductase

2WWR の概要

• エントリーDOI: 10.2210/pdb2wwr/pdb
• 関連するPDBエントリー: 2GCG 2H1S
• 分子名称: GLYOXYLATE REDUCTASE/HYDROXYPYRUVATE REDUCTASE, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: molecular conformation, oxidoreductase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 143526.06

構造登録者

Booth, M.P.S.,Conners, R.,Rumsby, G.,Brady, R.L. (登録日: 2009-10-26, 公開日: 2010-10-13, 最終更新日: 2023-12-20)

主引用文献

Booth, M.P.,Conners, R.,Rumsby, G.,Brady, R.L.
Structural Basis of Substrate Specificity in Human Glyoxylate Reductase/Hydroxypyruvate Reductase.
J.Mol.Biol., 360:178-, 2006

PubMed Abstract: Human glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the removal of the metabolic by-product glyoxylate from within the liver. Deficiency of this enzyme is the underlying cause of primary hyperoxaluria type 2 (PH2) and leads to increased urinary oxalate levels, formation of kidney stones and renal failure. Here we describe the crystal structure of human GRHPR at 2.2 A resolution. There are four copies of GRHPR in the crystallographic asymmetric unit: in each homodimer, one subunit forms a ternary (enzyme+NADPH+reduced substrate) complex, and the other a binary (enzyme+NADPH) form. The spatial arrangement of the two enzyme domains is the same in binary and ternary forms. This first crystal structure of a true ternary complex of an enzyme from this family demonstrates the relationship of substrate and catalytic residues within the active site, confirming earlier proposals of the mode of substrate binding, stereospecificity and likely catalytic mechanism for these enzymes. GRHPR has an unusual substrate specificity, preferring glyoxylate and hydroxypyruvate, but not pyruvate. A tryptophan residue (Trp141) from the neighbouring subunit of the dimer is projected into the active site region and appears to contribute to the selectivity for hydroxypyruvate. This first crystal structure of a human GRHPR enzyme also explains the deleterious effects of naturally occurring missense mutations of this enzyme that lead to PH2.

PubMed: 16756993
DOI: 10.1016/J.JMB.2006.05.018

実験手法

X-RAY DIFFRACTION (2.82 Å)