Aspartyl beta-hydroxylase: in vitro hydroxylation of a synthetic peptide based on the structure of the first growth factor-like domain of human factor IX.
beta-Hydroxylation of aspartic acid is a post-translational modification that occurs in several vitamin K-dependent coagulation proteins. By use of a synthetic substrate comprised of the first epidermal growth factor-like domain in human factor IX and either mouse L-cell extracts or rat liver microsomes as the source of enzyme, in vitro aspartyl beta-hydroxylation was accomplished. Aspartyl beta-hydroxylase appears to require the same cofactors as known alpha-ketoglutarate-dependent dioxygenases. The hydroxylation reaction proceeds with the same stereospecificity and occurs only at the aspartate corresponding to the position seen in vivo. Further purification and characterization of this enzymatic activity should now be possible.
Gronke
R S
RS
Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
VanDusen
W J
WJ
Garsky
V M
VM
Jacobs
J W
JW
Sardana
M K
MK
Stern
A M
AM
Friedman
P A
PA
D003653:Decarboxylation; D004220:Disulfides; D005164:Factor IX / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D007739:L Cells; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D004220:Disulfides; D007656:Ketoglutaric Acids; D010446:Peptide Fragments; D005164:Factor IX; D007501:Iron; D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase