New structural motifs on the chymotrypsin fold and their potential roles in complement factor B

被引:34
作者
Jing, H
Xu, YY
Carson, M
Moore, D
Macon, KJ
Volanakis, JE
Narayana, SVL [1 ]
机构
[1] Univ Alabama Birmingham, Ctr Macromol Crystallog, Sch Optometry, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Grad Program Biophys Sci, Birmingham, AL 35294 USA
[3] Univ Alabama Birmingham, Pharmaceut Design Program, Birmingham, AL 35294 USA
[4] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Dept Med, Birmingham, AL 35294 USA
[5] Biomed Sci Res Ctr A Fleming, Vari 16672, Greece
关键词
complement system; domain structure; factor B; protein-protein interaction; serine protease;
D O I
10.1093/emboj/19.2.164
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Factor B and C2 are two central enzymes for complement activation. They are multidomain serine proteases and require cofactor binding for full expression of proteolytic activities. We present a 2.1 Angstrom crystal structure of the serine protease domain of factor B, It shows a number of structural motifs novel to the chymotrypsin fold, which by sequence homology are probably present in C2 as well, These motifs distribute characteristically on the protein surface. Sis loops surround the active site, four of which shape substrate-binding pockets. Three loops nest to the oxyanion hole, which typically mediate zymogen activation, are much shorter or absent. Three insertions including the linker to the preceding domain bulge from the side opposite to the active site. The catalytic triad and non-specific substrate-binding site display active conformations, but the oxyanion hole displays a zymogen-like conformation. The bottom of the S1 pocket has a negative charge at residue 226 instead of the typical 189 position. These unique structural features may play different roles in domain-domain interaction, cofactor binding and substrate binding.
引用
收藏
页码:164 / 173
页数:10
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