1fdp

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spinqualitylabelsall models 1fdp, resolution 2.1Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

PROENZYME OF HUMAN COMPLEMENT FACTOR D, RECOMBINANT PROFACTOR D

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The crystal structure of profactor D, determined at 2.1 A resolution with, an Rfree and an R-factor of 25.1 and 20.4%, respectively, displays highly, flexible or disordered conformation for five regions: N-22, 71-76, 143-152, 187-193 and 215-223. A comparison with the structure of its, mature serine protease, complement factor D, revealed major conformational, changes in the similar regions. Comparisons with the zymogen-active enzyme, pairs of chymotrypsinogen, trypsinogen and prethrombin-2 showed a similar, distribution of the flexible regions. However, profactor D is the most, flexible of the four, and its mature enzyme displays inactive, self-inhibited active site conformation. Examination of the surface, properties of the N-terminus-binding pocket indicates that Ile16 may play, the initial positioning role for the N-terminus, and Leu17 probably also, helps in inducing the required conformational changes. This process, perhaps shared by most chymotrypsinogen-like zymogens, is followed by a, factor D-unique step, the re-orientation of an external Arg218 to an, internal position for salt-bridging with Asp189, leading to the generation, of the self-inhibited factor D.

Disease

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 Structure

1FDP is a Single protein structure of sequence from Homo sapiens. Active as Complement factor D, with EC number 3.4.21.46 Known structural/functional Sites: , , and . Full crystallographic information is available from OCA.

Reference

Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D., Jing H, Macon KJ, Moore D, DeLucas LJ, Volanakis JE, Narayana SV, EMBO J. 1999 Feb 15;18(4):804-14. PMID:10022823

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