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New structural motifs on the chymotrypsin fold and their potential roles in complement factor B
Author(s) -
Jing Hua,
Xu Yuanyuan,
Carson Mike,
Moore Dwight,
Macon Kevin J.,
Volanakis John E.,
Narayana Sthanam V.L.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.2.164
Subject(s) - oxyanion hole , zymogen , serine protease , binding site , active site , biology , chymotrypsin , serine , cofactor , catalytic triad , protein structure , biochemistry , stereochemistry , protease , enzyme , chemistry , trypsin
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 Å 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. Six loops surround the active site, four of which shape substrate‐binding pockets. Three loops next 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.