Structural highlights
Function
ASPH_HUMAN Isoform 1: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.[1] Isoform 8: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells.[2]
Publication Abstract from PubMed
Aspartate/asparagine-beta-hydroxylase (AspH) is a human 2-oxoglutarate (2OG) and Fe(II) oxygenase that catalyses C3 hydroxylations of aspartate/asparagine residues of epidermal growth factor-like domains (EGFDs). Unusually, AspH employs two histidine residues to chelate Fe(II) 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 Fe(II) 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.
Human Oxygenase Variants Employing a Single Protein Fe(II) Ligand Are Catalytically Active.,Brasnett A, Pfeffer I, Brewitz L, Chowdhury R, Nakashima Y, Tumber A, McDonough MA, Schofield CJ Angew Chem Int Ed Engl. 2021 Jun 21;60(26):14657-14663. doi: , 10.1002/anie.202103711. Epub 2021 May 19. PMID:33887099[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Srikanth S, Jew M, Kim KD, Yee MK, Abramson J, Gwack Y. Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A. 2012 May 29;109(22):8682-7. doi:, 10.1073/pnas.1200667109. Epub 2012 May 14. PMID:22586105 doi:10.1073/pnas.1200667109
- ↑ Srikanth S, Jew M, Kim KD, Yee MK, Abramson J, Gwack Y. Junctate is a Ca2+-sensing structural component of Orai1 and stromal interaction molecule 1 (STIM1). Proc Natl Acad Sci U S A. 2012 May 29;109(22):8682-7. doi:, 10.1073/pnas.1200667109. Epub 2012 May 14. PMID:22586105 doi:10.1073/pnas.1200667109
- ↑ 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. Angew Chem Int Ed Engl. 2021 Jun 21;60(26):14657-14663. PMID:33887099 doi:10.1002/anie.202103711
