Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, United Kingdom.
Biochem Biophys Res Commun. 2011 May 20;408(4):553-8. doi: 10.1016/j.bbrc.2011.04.059. Epub 2011 Apr 21.
Phytanoyl-CoA hydroxylase (PAHX) catalyzes an important step in the metabolism of the fatty acid side chain of chlorophyll. PHYHD1 exists in three isoforms and is the closest human homologue of PAHX. We show that like PAHX, the PHYHD1A but likely not the PHYHD1B/C isoforms, is a functional Fe(II) and 2-oxoglutarate (2OG) dependent oxygenase. Crystallographic and biochemical analyses reveal that PHYHD1A has the double-stranded β-helix fold and Fe(II) and cosubstrate binding residues characteristic of the 2-oxoglutarate dependent oxygenases and catalyzes the conversion of 2-oxoglutarate to succinate and CO(2) in an iron-dependent manner. However, PHYHD1A did not couple 2OG turnover to the hydroxylation of acyl-coenzyme A derivatives that are substrates for PAHX, implying that it is not directly involved in phytanoyl coenzyme-A metabolism.
植烷酰辅酶 A 羟化酶 (PAHX) 催化叶绿素脂肪酸侧链代谢中的一个重要步骤。PHYHD1 存在三种同工型，是 PAHX 最接近的人类同源物。我们表明，与 PAHX 一样，PHYHD1A 但可能不是 PHYHD1B/C 同工型，是一种功能性 Fe(II)和 2-氧戊二酸 (2OG) 依赖性加氧酶。晶体学和生化分析表明，PHYHD1A 具有双链 β-螺旋折叠和 Fe(II)和辅助因子结合残基，这些特征是 2-氧戊二酸依赖性加氧酶的特征，并以铁依赖性方式催化 2-氧戊二酸转化为琥珀酸和 CO(2)。然而，PHYHD1A 并没有将 2OG 周转与 PAHX 底物的酰基辅酶 A 衍生物的羟化偶联起来，这意味着它不直接参与植烷酰辅酶 A 的代谢。
