Structure of human factor D. A complement system protein at 2.0 A resolution.
Factor D, an essential enzyme for the activation of the alternative pathway of the complement system, belongs to the serine protease superfamily. The crystal structure of the enzyme was solved by a combination of multiple isomorphous replacement and molecular replacement methods. The present model was refined to an R-factor of 18.8% using 23,681 observed reflections between 7.5 and 2.0 A resolution, with a root-mean-square deviation from standard bond lengths of 0.016 A. The two non-crystallographically related molecules in the triclinic unit cell have distinctive active site conformations. The protein has the general structural fold of a serine protease, but there are several unique amino acid substitutions resulting in significant alterations in the critical loops responsible for catalysis and substrate specificity in serine proteases. Factor D is the first complement serine protease whose three-dimensional structure has been determined.
Narayana
S V
SV
Center for Macromolecular Crystallography, University of Alabama at Birmingham 35294.
Carson
M
M
el-Kabbani
O
O
Kilpatrick
J M
JM
Moore
D
D
Chen
X
X
Bugg
C E
CE
Volanakis
J E
JE
DeLucas
L J
LJ
D000595:Amino Acid Sequence; D011416:Complement Factor D / Q000737:chemistry*; D003460:Crystallization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
C493488:CFD protein, human; D011416:Complement Factor D