Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active
Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and FeII oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate FeII rather than the typical triad...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2021
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| _version_ | 1797054975332843520 |
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| author | Brasnett, A Pfeffer, I Brewitz, L Chowdhury, R Nakashima, Y Tumber, A McDonough, MA Schofield, CJ |
| author_facet | Brasnett, A Pfeffer, I Brewitz, L Chowdhury, R Nakashima, Y Tumber, A McDonough, MA Schofield, CJ |
| author_sort | Brasnett, A |
| collection | OXFORD |
| description | Aspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and FeII oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate FeII rather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its FeII binding histidine residues are substituted for alanine. Both the H725A and, in particular, the H679A AspH variants retain substantial catalytic activity. Crystal structures clearly reveal metal-ligation by only a single protein histidine ligand. The results have implications for the functional assignment of 2OG oxygenases and for the design of non-protein biomimetic catalysts. |
| first_indexed | 2024-03-06T19:04:54Z |
| format | Journal article |
| id | oxford-uuid:14ccdeeb-cd6b-4572-ba04-0605d01361c5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:04:54Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:14ccdeeb-cd6b-4572-ba04-0605d01361c52022-03-26T10:21:52ZHuman oxygenase variants employing a single protein Fe(II) ligand are catalytically activeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:14ccdeeb-cd6b-4572-ba04-0605d01361c5EnglishSymplectic ElementsWiley2021Brasnett, APfeffer, IBrewitz, LChowdhury, RNakashima, YTumber, AMcDonough, MASchofield, CJAspartate/asparagine-β-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and FeII oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate FeII rather than the typical triad of two histidine and one glutamate/aspartate residue. We report kinetic, inhibition, and crystallographic studies concerning human AspH variants in which either of its FeII binding histidine residues are substituted for alanine. Both the H725A and, in particular, the H679A AspH variants retain substantial catalytic activity. Crystal structures clearly reveal metal-ligation by only a single protein histidine ligand. The results have implications for the functional assignment of 2OG oxygenases and for the design of non-protein biomimetic catalysts. |
| spellingShingle | Brasnett, A Pfeffer, I Brewitz, L Chowdhury, R Nakashima, Y Tumber, A McDonough, MA Schofield, CJ Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active |
| title | Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active |
| title_full | Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active |
| title_fullStr | Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active |
| title_full_unstemmed | Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active |
| title_short | Human oxygenase variants employing a single protein Fe(II) ligand are catalytically active |
| title_sort | human oxygenase variants employing a single protein fe ii ligand are catalytically active |
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