1fdp
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystal structure of profactor D, determined at 2.1 A resolution with | + | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Delucas, L | + | [[Category: Delucas, L J.]] |
[[Category: Jing, H.]] | [[Category: Jing, H.]] | ||
| - | [[Category: Macon, K | + | [[Category: Macon, K J.]] |
[[Category: Moore, D.]] | [[Category: Moore, D.]] | ||
| - | [[Category: Narayana, S | + | [[Category: Narayana, S V.L.]] |
| - | [[Category: Volanakis, J | + | [[Category: Volanakis, J E.]] |
[[Category: complement]] | [[Category: complement]] | ||
[[Category: factor d]] | [[Category: factor d]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:37:40 2008'' |
Revision as of 10:37, 21 February 2008
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PROENZYME OF HUMAN COMPLEMENT FACTOR D, RECOMBINANT PROFACTOR D
Contents |
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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