1FDP

PROENZYME OF HUMAN COMPLEMENT FACTOR D, RECOMBINANT PROFACTOR D

1FDP の概要

• エントリーDOI: 10.2210/pdb1fdp/pdb
• 分子名称: PROENZYME OF COMPLEMENT FACTOR D (2 entities in total)
• 機能のキーワード: serine protease, complement, factor d, profactor d, zymogen, proenzyme, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P00746
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100586.53

構造登録者

Jing, H.,Macon, K.J.,Moore, D.,Delucas, L.J.,Volanakis, J.E.,Narayana, S.V.L. (登録日: 1998-12-03, 公開日: 1999-12-03, 最終更新日: 2024-11-20)

主引用文献

Jing, H.,Macon, K.J.,Moore, D.,DeLucas, L.J.,Volanakis, J.E.,Narayana, S.V.
Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D.
Embo J., 18:804-814, 1999

PubMed Abstract: 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.

PubMed: 10022823
DOI: 10.1093/emboj/18.4.804

実験手法

X-RAY DIFFRACTION (2.1 Å)