ArticlePloS one2009
Stringency of the 2-His-1-Asp active-site motif in prolyl 4-hydroxylase.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Unusual catalytic strategy by non-heme Fe(ii)/2-oxoglutarate-dependent aspartyl hydroxylase AspH.Chemical science · 2024Article
- Non-Native Anionic Ligand Binding and Reactivity in Engineered Variants of the Fe(II)- and α-Ketoglutarate-Dependent Oxygenase, SadA.Inorganic chemistry · 2022Article
- Reaction pathway engineering converts a radical hydroxylase into a halogenase.Nature chemical biology · 2022Article
- Chloride Supports OInorganic chemistry · 2018Article
- P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon, bone, muscle and the eye.Human molecular genetics · 2017Article
- Structure-Guided Reprogramming of a Hydroxylase To Halogenate Its Small Molecule Substrate.Biochemistry · 2017Article
- Prolyl 4-Hydroxylase: Substrate Isosteres in Which an (E)- or (Z)-Alkene Replaces the Prolyl Peptide Bond.Biochemistry · 2017Article
- Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution.Angewandte Chemie (International ed. in English) · 2015Review
- Toxicogenomic effect of nickel and beyond.Archives of toxicology · 2014Review
- Bioavailable affinity label for collagen prolyl 4-hydroxylase.Bioorganic & medicinal chemistry · 2013Article
- Prolyl 4-hydroxylase.Critical reviews in biochemistry and molecular biology · 2010Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His-1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C-H bonds. Prolyl 4-hydroxylase (P4H) is an alpha-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His-1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change.
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Registered trials
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