1dfp: Difference between revisions

==Overview==

Factor D (D) is a serine protease, crucial for the activation of the, alternative complement pathway. Only a limited number of general serine, protease inhibitors are known to inhibit D, most of which covalently bind, to the serine hydroxyl of the catalytic triad. The structure of the first, enzyme:inhibitor covalent adduct of D with diisopropyl fluorophosphate, (DIP:D) to a resolution of 2.4 A is described. The inhibited enzyme is, similar in overall structure to the native enzyme and to trypsin, yet, exhibits notable differences in the active site. One region of the active, site is conserved between D and trypsin with respect to amino-acid, sequence and to conformation. Another reflects the amino-acid, substitutions and conformational flexibility between these enzymes. The, active-site histidine residue is observed in the gauche+ conformation, not, the normal gauche- orientation seen in the classic catalytic triad, arrangement required for enzymatic activity in serine proteases., Comparisons of the active sites between native D, the DIP:D adduct, and, DIP-inhibited trypsin have provided fundamental insights currently being, employed in the design of novel small-molecule pharmaceutical agents, capable of modulating the alternative complement pathway.

==About this Structure==

[[Category: serine protease]]