scholarly journals Substrate recognition by the vitamin k-dependent γ-glutamyl carboxylase: Identification of a sequence homology between the carboxylase and the carboxylase recognition site in the substrate

1993 ◽  
Vol 2 (11) ◽  
pp. 1987-1988 ◽  
Author(s):  
Paul A. Price ◽  
Matthew K. Williamson
Keyword(s):  
Vitamin K ◽  
Sequence Homology ◽  
Substrate Recognition ◽  
Recognition Site

Substrate Recognition by Vitamin K-Dependent Carboxylase

1987 ◽  
Vol 57 (01) ◽  
pp. 017-019 ◽  
Author(s):  
Magda M W Ulrich ◽  
Berry A M Soute ◽  
L Johan M van Haarlem ◽  
Cees Vermeer
Keyword(s):  
Amino Acid ◽  
Vitamin K ◽  
Substrate Recognition ◽  
Bovine Liver ◽  
Amino Acid Residues

SummaryDecarboxylated osteocalcins were prepared and purified from bovine, chicken, human and monkey bones and assayed for their ability to serve as a substrate for vitamin K-dependent carboxylase from bovine liver. Substantial differences were observed, especially between bovine and monkey d-osteocalcin. Since these substrates differ only in their amino acid residues 3 and 4, it seems that these residues play a role in the recognition of a substrate by hepatic carboxylase.

The Role of Cytochrome 2B1 Substrate Recognition Site Residues 115, 294, 297, 298, and 362 in the Oxidation of Steroids and 7-Alkoxycoumarins

2001 ◽  
Vol 394 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Tammy L. Domanski ◽  
You-Qun He ◽  
Emily E. Scott ◽  
Qinmi Wang ◽  
James R. Halpert
Keyword(s):  
Substrate Recognition ◽  
Recognition Site

scholarly journals The γ-Carboxylation Recognition Site Is Sufficient to Direct Vitamin K-dependent Carboxylation on an Adjacent Glutamate-rich Region of Thrombin in a Propeptide-Thrombin Chimera

1997 ◽  
Vol 272 (45) ◽  
pp. 28258-28262 ◽  
Author(s):  
Barbara C. Furie ◽  
Jennifer V. Ratcliffe ◽  
Jonathan Tward ◽  
Maria J. Jorgensen ◽  
Lawrence S. Blaszkowsky ◽  
...  
Keyword(s):  
Vitamin K ◽  
Recognition Site ◽  
Rich Region

scholarly journals Structural Determinants of Aromatase Cytochrome P450 Inhibition in Substrate Recognition Site-1

2002 ◽  
Vol 16 (7) ◽  
pp. 1456-1468 ◽  
Author(s):  
Alan Conley ◽  
Samantha Mapes ◽  
C. Jo Corbin ◽  
Douglas Greger ◽  
Sandra Graham
Keyword(s):  
Cytochrome P450 ◽  
Substrate Recognition ◽  
Recognition Site ◽  
Structural Determinants

Analysis of Substrate Recognition Site 2 (SRS2) in human cytochrome P450 1A2 using whole-plasmid random mutagenesis

2013 ◽  
Vol 9 (1) ◽  
pp. 9-14
Author(s):  
Joohwan Kim ◽  
Songhee Han ◽  
Seunghye Choi ◽  
Hyoung-Goo Park ◽  
Young-Ran Lim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Recognition ◽  
Random Mutagenesis ◽  
Recognition Site ◽  
Cytochrome P450 1A2 ◽  
Human Cytochrome

Phenylalanine and Tryptophan Scanning Mutagenesis of CYP3A4 Substrate Recognition Site Residues and Effect on Substrate Oxidation and Cooperativity†

Biochemistry ◽  
2001 ◽  
Vol 40 (34) ◽  
pp. 10150-10160 ◽  
Author(s):  
Tammy L. Domanski ◽  
You-Ai He ◽  
Kishore K. Khan ◽  
Fabienne Roussel ◽  
Qinmi Wang ◽  
...  
Keyword(s):  
Substrate Recognition ◽  
Substrate Oxidation ◽  
Recognition Site ◽  
Cyp3a4 Substrate

VITAMIN K-DEPENDENT γ-CARBOXYLATION OF FACTOR IX REQUIRES A RECOGNITION SITE CONTAINED WITHIN THE PROPEPTIDE

1987 ◽  
Author(s):  
M J Jorgensen ◽  
MJ Rabiet ◽  
A B Cantor ◽  
B Furie ◽  
C L Brown ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Vitamin K ◽  
Chinese Hamster Ovary Cells ◽  
Recognition Site ◽  
Factor Ix ◽  
Terminal Sequence ◽  
Specific Antibodies ◽  
Amino Terminal ◽  
Rich Domain ◽  
Made In

The vitamin K-dependent proteins, including Factor IX (FIX), are calcium-binding proteins that undergo vitamin K-dependent post-translational modification to convert amino terminal glutamic aoid residues to Gla residues. Sequence homology among the propeptides of these proteins suggests a role for this region in designating the adjacent glutamic acid-rich domain for γ-carboxylation during intraoellular processing. Mutations vere made in the propeptide (residues -1 to -18) of FIX, and the effects on γ-carboxylation were assessed. The human FIX cDNA coding sequenoe was modified using oligonucleotide-directed site-specific mutagenesis and was expressed in Chinese hamster ovary cells. The extent of γ-carboxylation of secreted FIX was determined by (1) ability to interact with conformation-specific antibodies directed against the Gla-dependent, metal-stabilized, native structure of FIX, and (2) direct Gla analysis of the alkaline hydrolysate. Using the unmodified coding sequence, 64 ± 17 % of recombinant Factor IX bound to the conformation-specific antibodies, and 9.4 ± 0.7 Gla residues were found (compared with 12 Gla in plasma FIX). When the 18-residue propeptide was deleted, secreted FIX contained no detectable native FIX antigen and no detectable Gla. Similarly, point mutations leading to substitution of Ala for Phe at residue -16 or Glu for Ala at residue -10 led to secretion of FIX containing 2% and 6% native antigen, respectively, and approximately 1-2 Gla residues. The molecular weight of each of the reoombinant FIX species, as estimated by SDS-PAGE, was identical to that of plasma FIX. NH2-terminal sequence analysis of the mutant FIX speoies yielded the NH2-terminal sequence of plasma FIX. These data indicate that the mutations made in the propeptide did not interfere with intracellular proteolytic prooessing of FIX. We conolude that the FIX propeptide participates in defining a recognition site that designates an adjacent glutamic acid-rich domain for γ-carboxylation. The association of the propeptide with the γ-carboxylation recognition site provides the first demonstration of a specific function served by a propeptide in post-translational protein processing.

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