Substrate Selectivity Analyses of Factor Inhibiting Hypoxia-Inducible Factor

Substrate specificity: Biochemical and crystallographic analyses reveal the hypoxia‐inducible factor hydroxylase (FIH) as being promiscuous with respect to the residues that it can hydroxylate in β‐position, which in addition to Asn, Asp, and His include Leu and Ser residues. The Ser substrate is ox...

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Published inAngewandte Chemie (International ed.) Vol. 52; no. 6; pp. 1700 - 1704
Main Authors Yang, Ming, Hardy, Adam P., Chowdhury, Rasheduzzaman, Loik, Nikita D., Scotti, John S., McCullagh, James S. O., Claridge, Timothy D. W., McDonough, Michael A., Ge, Wei, Schofield, Christopher J.
Format Journal Article
LanguageEnglish
Published Weinheim WILEY-VCH Verlag 04.02.2013
WILEY‐VCH Verlag
Wiley Subscription Services, Inc
EditionInternational ed. in English
Subjects
Amino Acid Sequence
amino acids
Ankyrins - analysis
Ankyrins - chemistry
Binding Sites
Biocatalysis
Biochemistry
Catalytic Domain
Crystallography
Diols
enzymes
Hydroxylation
Hypoxia-Inducible Factor 1 - antagonists & inhibitors
Hypoxia-Inducible Factor 1 - metabolism
Magnetic Resonance Spectroscopy
Molecular Sequence Data
oxidation
oxygenase
Peptides - metabolism
Pictures
Residues
Selectivity
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Substrate Specificity
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Summary:Substrate specificity: Biochemical and crystallographic analyses reveal the hypoxia‐inducible factor hydroxylase (FIH) as being promiscuous with respect to the residues that it can hydroxylate in β‐position, which in addition to Asn, Asp, and His include Leu and Ser residues. The Ser substrate is oxidized to an epimeric β‐geminal diol product (see picture).
Bibliography:ArticleID:ANIE201208046
We thank M. Jiang for amino acid standards; H. Tarhonskaya for the FIH specific activity measurement; the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the European Research Council for funding and Diamond Light Source for access to beamline IO3.
ark:/67375/WNG-JVR9R20P-4
European Research Council
istex:556D86452555D2389AB971D69EEAA9BD6845FD9B
Wellcome Trust
Biotechnology and Biological Sciences Research Council
These authors contributed equally to this work.
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SourceType-Scholarly Journals-1
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ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201208046