1dst
MUTANT OF FACTOR D WITH ENHANCED CATALYTIC ACTIVITY
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OverviewOverview
Complement factor D is a serine protease regulated by a novel mechanism, that depends on conformational changes rather than cleavage of a zymogen, for expression of proteolytic activity. The conformational changes are, presumed to be induced by the single natural substrate, C3bB, and to, result in reversible reorientation of the catalytic center and of the, substrate binding site of factor D, both of which have atypical, conformations. Here we report that replacement of Ser94, Thr214, and, Ser215 of factor D (chymotrypsinogen numbering has been used for, comparison purposes) with the corresponding residues of trypsin, Tyr, Ser, and Trp, is sufficient to induce substantially higher catalytic activity, associated with a typical serine protease alignment of the catalytic triad, residues His57, Asp102, and Ser195. These results provide a partial, structural explanation for the low reactivity of "resting-state" factor D, toward synthetic substrates.
DiseaseDisease
Known diseases associated with this structure: Azoospermia OMIM:[400005], Complement factor D deficiency OMIM:[134350], Corneal fleck dystrophy OMIM:[609414], Properdin deficiency, X-linked OMIM:[300383]
About this StructureAbout this Structure
1DST is a Single protein structure of sequence from Homo sapiens. Active as Complement factor D, with EC number 3.4.21.46 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of a complement factor D mutant expressing enhanced catalytic activity., Kim S, Narayana SV, Volanakis JE, J Biol Chem. 1995 Oct 13;270(41):24399-405. PMID:7592653
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