Biochemical and Structural Insights into FIH-Catalysed Hydroxylation of Transient Receptor Potential Ankyrin Repeat Domains

被引：0
作者：
Saward, Benjamin G. [1 ,2 ]
Leissing, Thomas M. [1 ,2 ]
Clifton, Ian J. [1 ,2 ]
Tumber, Anthony [1 ,2 ]
Timperley, Christopher M. [3 ]
Hopkinson, Richard J. [1 ,2 ,4 ,5 ]
Schofield, Christopher J. [1 ,2 ]
机构：
[1] Univ Oxford, Dept Chem, Mansfield Rd, Oxford OX1 3TA, England
[2] Univ Oxford, Ineos Oxford Inst Antimicrobial Res, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England
[3] Def Sci & Technol Lab DSTL, CBR Div, Salisbury SP4 0JQ, England
[4] Univ Leicester, Leicester Inst Struct & Chem Biol, Henry Wellcome Bldg, Lancaster Rd, Leicester LE1 7RH, England
[5] Univ Leicester, Sch Chem, Henry Wellcome Bldg,Lancaster Rd, Lancaster LE1 7RH, England
来源：
CHEMBIOCHEM | 2023年 / 24卷 / 04期
基金：
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词：
ankyrin; factor inhibiting HIF (FIH); hypoxia inducible factor HIF; oxygenases; demethylases; post translational modifications; transient receptor potential (TRP) channel; ASPARAGINYL HYDROXYLATION; BETA-HYDROXYLATION; HYPOXIA; TRPA1; CHANNEL; NOTCH; MECHANISM; TRPV3;
D O I：
10.1002/cbic.202200576
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Transient receptor potential (TRP) channels have important roles in environmental sensing in animals. Human TRP subfamily A member 1 (TRPA1) is responsible for sensing allyl isothiocyanate (AITC) and other electrophilic sensory irritants. TRP subfamily vanilloid member 3 (TRPV3) is involved in skin maintenance. TRPV3 is a reported substrate of the 2-oxoglutarate oxygenase factor inhibiting hypoxia-inducible factor (FIH). We report biochemical and structural studies concerning asparaginyl hydroxylation of the ankyrin repeat domains (ARDs) of TRPA1 and TRPV3 catalysed by FIH. The results with ARD peptides support a previous report on FIH-catalysed TRPV3 hydroxylation and show that, of the 12 potential TRPA1 sequences investigated, one sequence (TRPA1 residues 322-348) undergoes hydroxylation at Asn336. Structural studies reveal that the TRPA1 and TRPV3 ARDs bind to FIH with a similar overall geometry to most other reported FIH substrates. However, the binding mode of TRPV3 to FIH is distinct from that of other substrates.
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页数：7
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