A chymotrypsin inhibitor, designated NA-CI, was isolated from the venom of the Chinese cobra Naja atra by three-step chromatography. It inhibited bovine alpha-chymotrypsin with a Ki of 25 nM. The molecular mass of NA-CI was determined to be 6403.8 Da by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) analysis. The complete amino acid sequence was determined after digestion of S-carboxymethylated inhibitor with Staphylococcus aureus V8 protease and porcine trypsin. NA-CI was a single polypeptide chain composed of 57 amino acid residues. The main contact site with the protease (P1) has a Phe, showing the specificity of the inhibitor. NA-CI shared great similarity with the chymotrypsin inhibitor from Naja naja venom (identities=89.5%) and other snake venom protease inhibitors.
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http://dx.doi.org/10.1016/j.cbpc.2003.11.007 | DOI Listing |
Fertil Steril
January 2025
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104 USA. Electronic address:
Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown.
Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189.
J Thromb Haemost
January 2025
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104 USA. Electronic address:
Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown.
Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189.
ACS Catal
December 2024
Departments of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, United States.
Antimicrob Agents Chemother
December 2024
Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
This study evaluated the safety and pharmacokinetics (PK) of a single dose of leritrelvir, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in patients with hepatic impairment versus healthy participants with normal hepatic function. Eight participants with mild (Child-Pugh A) hepatic impairment, eight with moderate (Child-Pugh B) hepatic impairment, and eight healthy matched control participants were enrolled in this open-label, parallel clinical trial. After administration of leritrelvir of 400 mg, PK parameters were calculated and compared across groups.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Wellcome Centre for Anti-Infectives Research, University of Dundee, Dundee, UK. Electronic address:
The proteasome is considered an excellent drug target for many infectious diseases as well as cancer. Challenges with robust and safe supply of proteasomes from infectious agents, lack of structural information, and complex pharmacology due to multiple active sites have hampered progress in the infectious disease space. We recombinantly expressed the proteasome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, and demonstrate pharmacological equivalence to the native T.
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