Distinct multisite synergistic interactions determine substrate specificities of human chymase and rat chymase-1 for angiotensin II formation and degradation.

The Journal of Biological Chemistry
S SankerAhsan Husain

Abstract

Human chymase and rat chymase-1 are mast cell serine proteases involved in angiotensin II (Ang II) formation and degradation, respectively. Previous studies indicate that both these enzymes have similar P1 and P2 preferences, which are the major determinants of specificity. Surprisingly, despite the occurrence of optimal P2 and P1 residues at the Phe8 downward arrow and Tyr4 downward arrow bonds (where downward arrow, indicates the scissile bond in peptide substrates) in Ang I (DRVYIHPFHL), human chymase cleaves the Phe8 downward arrow bond with an approximately 750-fold higher catalytic efficiency (kcat/Km) than the Tyr4 downward arrow bond in Ang II (DRVYIHPF), whereas rat chymase-1 cleaves the Tyr4 downward arrow bond with an approximately 20-fold higher catalytic efficiency than the Phe8 downward arrow bond. Differences in the acyl groups IHPF and DRVY at the Phe8 downward arrow and Tyr4 downward arrow bonds, respectively, are chiefly responsible for the preference of human chymase for the Phe8 downward arrow bond. We show that the IHPF sequence forms an optimal acyl group, primarily through synergistic interactions between neighboring acyl group residues. In contrast to human chymase, rat chymase-1 shows a preference for t...Continue Reading

References

Sep 22, 1992·Biochemistry·H Grøn, K Breddam
Aug 1, 1991·European Journal of Biochemistry·V SchellenbergerH D Jakubke
Sep 18, 1990·Biochemistry·J A Wells
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·H Le TrongR G Woodbury
Apr 20, 1967·Biochemical and Biophysical Research Communications·I Schechter, A Berger
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·M BastosR H Abeles
Apr 1, 1993·The Journal of Clinical Investigation·H UrataA Husain
Jan 26, 1996·Science·U M ChandrasekharanA Husain
Feb 23, 1996·The Journal of Biological Chemistry·G S CoombsD R Corey
Sep 1, 1959·The Journal of Experimental Medicine·E P BENDITT, M ARASE

❮ Previous
Next ❯

Citations

Mar 16, 2001·Clinica Chimica Acta; International Journal of Clinical Chemistry·S TakaiM Miyazaki
May 15, 2002·Biochimica Et Biophysica Acta·Diego J MuilenburgGeorge H Caughey
Aug 28, 1999·Bioorganic & Medicinal Chemistry Letters·W C GroutasJ Tu
Apr 5, 2003·The International Journal of Biochemistry & Cell Biology·Stefan EngeliArya M Sharma
Jul 3, 2004·The Journal of Clinical Investigation·Ming LiAhsan Husain
Mar 20, 2001·The Journal of Clinical Investigation·C GuoM Rabinovitch
Jan 21, 2014·European Journal of Pharmacology·Daniele De FilippisTeresa Iuvone
Jan 4, 1998·Kidney International·R Ardaillou, D Chansel
Aug 2, 2005·Biochimica Et Biophysica Acta·Qingyu WuGary Gang Deng
Nov 19, 2011·Toxicon : Official Journal of the International Society on Toxinology·Alexandre Kazuo KuniyoshiFernanda Calheta Vieira Portaro
Jul 7, 2015·BioMed Research International·Devandir Antonio de Souza JuniorMaria Celia Jamur
Oct 11, 2003·Molecular Cell·Merridee A WoutersAhsan Husain
Jul 14, 2007·Circulation Research·Eduard N LavrentyevKafait U Malik
Dec 14, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Jacob JosephMartin Hauer-Jensen
Mar 11, 2008·Genesis : the Journal of Genetics and Development·Werner MüschThomas Hehlgans
Aug 2, 2002·Current Opinion in Cardiology·Louis J Dell'Italia, Ahsan Husain
Jun 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·K A LindstedtP T Kovanen
Aug 28, 2002·The Journal of Biological Chemistry·Petra Schling, Thorsten Schäfer
Oct 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wilfred W RaymondGeorge H Caughey
Nov 15, 1997·The American Journal of Physiology·E BalcellsL J Dell'Italia
Apr 26, 2002·Journal of Cardiovascular Pharmacology·Carlos F SantosAndrew S Greene
Jan 1, 2020·International Journal of Molecular Sciences·Yuan ZhongweiLars Hellman
Nov 30, 2011·Drug Discovery Today. Disease Models·Hongyan Dai, Ronald J Korthuis

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.