Effect of the?-amino acid radical on the cleavage rate of the carbocyclohexyloxy group during hydro brominolysis

1966 ◽  
Vol 15 (5) ◽  
pp. 883-885
Author(s):  
V. A. Shibnev ◽  
K. T. Poroshin ◽  
V. S. Grechishko ◽  
A. V. Lisovenko
Keyword(s):  
Amino Acid ◽  
Cleavage Rate ◽  
Acid Radical

Substrate Preferences for Antiplasmin Cleaving Enzyme Hydrolysis of Peptides Derived from the α2-Antiplasmin Sequence.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1704-1704
Author(s):  
Kenneth W. Jackson ◽  
Victoria J. Christiansen ◽  
Kyung N. Lee ◽  
Christina F. Mason ◽  
Patrick A. McKee
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Enzyme Hydrolysis ◽  
Peptide Sequence ◽  
Peptide Hydrolysis ◽  
Cleavage Rate ◽  
Amino Terminal ◽  
Substrate Preferences ◽  
Polymorphic Position ◽  
Hydrolysis Of

Abstract Antiplasmin cleaving enzyme (APCE) is a proteinase that specifically, but slowly cleaves the Pro-Asn bond in long-form α2-antiplasmin (Met-α2AP) in human plasma. This slow cleavage produces a steady-state plasma mixture of Met-α2AP and an N-terminally shortened form of antiplasmin, Asn-α2AP. The Asn-α2AP form crosslinks to fibrin ~13-fold faster than Met-α2AP. A faster crosslink rate causes a greater number of antiplasmin molecules to become bound during fibrin formation, thereby enhancing resistance to fibrinolysis. Inhibition of plasma APCE may decrease the number of antiplasmin molecules crosslinked and result in clots that are more easily removed during fibrinolysis. Therefore, an inhibitor specific for APCE could potentially be used to regulate fibrinolysis. Human Met-α2AP exists in two polymorphic forms at position six in the mature sequence, with arginine predominant, and tryptophan accounting for a lesser percentage. We have determined the relative cleavage rates of synthetic peptides from a peptide library that span the cleavage site. The peptides contained all common amino acids except cysteine in the polymorphic position (P7 position). Arg was the optimal amino acid in this position with a relative cleavage rate ~5–10-fold faster than other amino acids except Lys, which was ~70% of the Arg rate. The P7 position Arg enhancement was also observed when Arg was in the P6 or P5 position, but no enhancement was observed when Arg was moved to positions P8, P4, P3 or P2. It was also determined that APCE is preferentially an endoproteinase rather than an aminodipeptidase, with a 10-fold greater rate of hydrolysis of the internal Pro-Asn bond in the Met-α2AP 1–17 peptide sequence MEPLGRQLTSGP-NQEQV over the Pro-Asn bond penultimate to the amino-terminal bond in the Met-α2AP 11–27 peptide sequence GP-NQEQVSPLTLLKLGN in peptide hydrolysis experiments. We conclude that APCE inhibitors designed with a positive charge placed upstream of the Pro-X scissile bond equivalent to five to seven amino acid residues may prove to be highly potent and specific. In addition, such inhibitors should also prove useful for blocking the activity of the closely related enzyme fibroblast activation protein. This work was supported by NIH grant HL072995.

scholarly journals Stephan Oroszlan and the Proteolytic Processing of Retroviral Proteins: Following A Pro

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2218
Author(s):  
Ronald Swanstrom ◽  
Wesley I. Sundquist
Keyword(s):  
Amino Acid ◽  
Proteolytic Processing ◽  
Multiple Roles ◽  
Terminal Amino Acid ◽  
Cleavage Rate ◽  
Viral Protease ◽  
Amino Terminal ◽  
Protease Cleavage ◽  
Processing Site ◽  
Terminal Amino

Steve Oroszlan determined the sequences at the ends of virion proteins for a number of different retroviruses. This work led to the insight that the amino-terminal amino acid of the mature viral CA protein is always proline. In this remembrance, we review Steve’s work that led to this insight and show how that insight was a necessary precursor to the work we have done in the subsequent years exploring the cleavage rate determinants of viral protease processing sites and the multiple roles the amino-terminal proline of CA plays after protease cleavage liberates it from its position in a protease processing site.

scholarly journals Turning on ribonucleotide reductase by light-initiated amino acid radical generation

2004 ◽  
Vol 101 (18) ◽  
pp. 6882-6887 ◽  
Author(s):  
M. C. Y. Chang ◽  
C. S. Yee ◽  
J. Stubbe ◽  
D. G. Nocera
Keyword(s):  
Amino Acid ◽  
Ribonucleotide Reductase ◽  
Acid Radical ◽  
Radical Generation

Metal-Mediated Formation of Gas-Phase Amino Acid Radical Cations†,#

2006 ◽  
Vol 110 (27) ◽  
pp. 8304-8315 ◽  
Author(s):  
Christopher K. Barlow ◽  
Damian Moran ◽  
Leo Radom ◽  
W. David McFadyen ◽  
Richard A. J. O'Hair
Keyword(s):  
Amino Acid ◽  
Gas Phase ◽  
Radical Cations ◽  
Acid Radical

scholarly journals Exploring amino-acid radical chemistry: protein engineering and de novo design

2005 ◽  
Vol 1707 (1) ◽  
pp. 103-116 ◽  
Author(s):  
Kristina Westerlund ◽  
Bruce W. Berry ◽  
Heidi K. Privett ◽  
Cecilia Tommos
Keyword(s):  
Amino Acid ◽  
Protein Engineering ◽  
De Novo ◽  
De Novo Design ◽  
Radical Chemistry ◽  
Acid Radical
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