Crystal structure of PHYHD1A, a 2OG oxygenase related to phytanoyl-CoA hydroxylase |
| |
| Authors: | Zhang Zhihong Kochan Grazyna T Ng Stanley S Kavanagh Kathryn L Oppermann Udo Schofield Christopher J McDonough Michael A |
| |
| Affiliation: | aChemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom;bStructural Genomics Consortium, Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom;cThe Botnar Research Centre, NIHR Oxford Biomedical Research Unit, Oxford OX3 7LD, United Kingdom |
| |
| Abstract: | 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 CO2 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. |
| |
| Keywords: | Abbreviations: ARD, adult Refsum disease DSBH, double-stranded beta-helix EctD, ectoine hydroxylase FIH, factor inhibiting hypoxia-inducible factor 2OG, 2-oxoglutarate PAHX, phytanoyl-CoA hydroxylase PHD2, prolyl hydroxylase isoform 2 SyrB2, 2OG dependent halogenase |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
