title: Structure and function of complement C5 convertase enzymes.
abstract: The multisubunit enzymes of the complement system that cleave C5 have many unusual properties, the most striking of which is that they acquire their specificity for C5 following cleavage of another substrate C3. C5 convertases are assemblies of two proteins C4b and C2a (classical or lectin pathways) or C3b and Bb (alternative pathway) and additional C3b molecules. The catalytic complexes (C4b, C2a or C3b, Bb) are intrinsically unstable ( t (1/2)=1-3 min) and the enzymes are controlled by numerous regulatory proteins that accelerate this natural decay rate. Immediately after assembly, the bi-molecular enzymes preferentially cleave the protein C3 and exhibit poor activity toward C5 (a K (m) of approx. 25 microM and a C5 cleavage rate of 0.3-1 C5/min at V (max)). Efficient C3 activation results in the covalent attachment of C3b to the cell surface and to the enzyme itself, resulting in formation of C3b-C3b and C4b-C3b complexes. Our studies have shown that deposition of C3b alters the specificity of the enzymes of both pathways by changing the K (m) for C5 more than 1000-fold from far above the physiological C5 concentration to far below it. Thus, after processing sufficient C3 at the surface of a microorganism, the enzymes switch to processing C5, which initiates the formation of the cytolytic membrane attack complex of complement.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center, Tyler 75708, USA. michael.pangbum@uthct.edu
authors.forename: M K
authors.initials: MK
authors.lastname: Pangburn
authors.forename: N
authors.initials: N
authors.lastname: Rawal
mesh_terms: D000818:Animals; D050577:Complement C3-C5 Convertases / Q000737:chemistry* / Q000378:metabolism*; D003182:Complement C5 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D003182:Complement C5; D050577:Complement C3-C5 Convertases