C5 convertase of the alternative pathway of complement. Kinetic analysis of the free and surface-bound forms of the enzyme.

The Journal of Biological Chemistry
Nenoo Rawal, M K Pangburn

Abstract

Although proteolytic activation of the complement protein C5 initiates important defensive and occasionally pathological inflammatory reactions, the enzymatic properties of the enzymes responsible for this cleavage have never been examined. We have studied the kinetic parameters of the C5 convertase of the alternative pathway of complement, either bound to a zymosan surface or in its monomeric soluble form. C5 convertase enzymatic activity was measured as a function of C5 concentration by quantitating production of C5b,6 under physiological conditions of temperature, pH, and ionic strength. The C5 convertases appeared to follow Michaelis-Menten kinetics and exhibited similar catalytic rate constants (kcat). However, the surface-bound enzyme, ZymC3b,Bb had a Km (1.4 microM) that was 17 times lower than that of the soluble monomeric form of the enzyme, C3b,Bb (Km = 24 microM). The kcat for the cell-bound enzyme, ZymC3b,Bb was 0.0048 s-1 and that for soluble C3b,Bb was 0.0110 s-1. Both forms of the enzyme had a low turnover number at Vmax (0.23 to 0.68 C5/min/enzyme). Substituting Mg2+ for Ni2+ did not alter the kinetic parameters but lowered the half-life of the enzyme by 5-7-fold. The kinetic data presented demonstrate that the ...Continue Reading

References

Feb 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·R G MedicusH J Müller-Eberhard
Apr 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·D T Fearon, K F Austen
May 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·M K Pangburn, H J Müller-Eberhard
Oct 19, 1990·Journal of Immunological Methods·C W Van den BergH Van Dijk
Jan 1, 1990·International Journal of Immunopharmacology·A C IssekutzR A Patrick
Jun 1, 1987·The Journal of Experimental Medicine·Y TakataK Inoue
Jan 1, 1974·The Journal of Experimental Medicine·O Götze, H J Müller-Eberhard
Jan 1, 1983·Methods in Enzymology·R I Christopherson
Dec 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·C W Vogel, H J Müller-Eberhard
Aug 1, 1995·Nature Medicine·L A Matis, S A Rollins
Jan 1, 1994·Annual Review of Pharmacology and Toxicology·J W Homeister, B R Lucchesi
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S W Santoro, G F Joyce

❮ Previous
Next ❯

Citations

Jan 5, 2002·Cytometry·Merav SunrayMordechai Deutsch
May 23, 2001·International Immunopharmacology·N Rawal, M K Pangburn
Feb 7, 2009·The Journal of Biological Chemistry·Kenneth J KatschkeChristian Wiesmann
Sep 26, 2007·The Journal of Experimental Medicine·Ilse JongeriusSuzan H M Rooijakkers
Nov 19, 2010·Bioanalysis·Bing KuangHuifen Faye Wang
Apr 15, 2016·EBioMedicine·Jonathan H FoleyEdward M Conway
Jun 7, 2015·Journal of the American Society of Nephrology : JASN·Marieta M RusevaMatthew C Pickering
Apr 27, 2010·Toxicon : Official Journal of the International Society on Toxinology·Carl-Wilhelm Vogel, David C Fritzinger
Sep 19, 2006·Molecular Immunology·Nenoo Rawal, Michael K Pangburn
Nov 11, 2015·BMC Biology·Evelien T M BerendsSuzan H M Rooijakkers
Jul 3, 2013·Molecular Immunology·Allison M LesherWen-Chao Song
Dec 18, 2013·Blood·Jovian M WatEdward M Conway
Oct 27, 2016·Immunological Reviews·Janus A Schatz-JakobsenGregers R Andersen
Apr 1, 2016·PloS One·Nehemiah ZewdeDimitrios Morikis
Jul 25, 2003·The Journal of Biological Chemistry·Nenoo Rawal, Michael K Pangburn
Sep 28, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kaibin ShiYaping Yan
Oct 20, 2006·Nature·Christian WiesmannMenno van Lookeren Campagne
Jul 22, 2018·The Journal of Biological Chemistry·Alex MacphersonAlastair D G Lawson
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Viviana P FerreiraMichael K Pangburn
May 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Viviana P FerreiraDavid Kavanagh
Jun 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masashi MizunoSeiichi Matsuo
Feb 18, 2012·American Journal of Physiology. Renal Physiology·Masashi MizunoB Paul Morgan
May 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gurpanna SagguViviana P Ferreira
Sep 2, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Apostolos GeorgiannakisStephen E Moss
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·N Rawal, M Pangburn
May 10, 2019·Frontiers in Immunology·Fernando CorvilloMargarita López-Trascasa
Jan 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·N Rawal, M K Pangburn
Apr 26, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M K PangburnA K Sharma
Mar 19, 2020·Molecular Medicine Reports·Han Xue JiangWei Jing Liu
Oct 6, 2020·Frontiers in Immunology·Alexander TilleMarc Thilo Figge

❮ 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.

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

Anaphylaxis

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.