1fdp
From Proteopedia
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|SITE= <scene name='pdbsite=TRA:Catalytic+Triad'>TRA</scene>, <scene name='pdbsite=TRB:Catalytic+Triad'>TRB</scene>, <scene name='pdbsite=TRC:Catalytic+Triad'>TRC</scene> and <scene name='pdbsite=TRD:Catalytic+Triad'>TRD</scene> | |SITE= <scene name='pdbsite=TRA:Catalytic+Triad'>TRA</scene>, <scene name='pdbsite=TRB:Catalytic+Triad'>TRB</scene>, <scene name='pdbsite=TRC:Catalytic+Triad'>TRC</scene> and <scene name='pdbsite=TRD:Catalytic+Triad'>TRD</scene> | ||
|LIGAND= | |LIGAND= | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Complement_factor_D Complement factor D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.46 3.4.21.46] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Complement_factor_D Complement factor D], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.46 3.4.21.46] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fdp OCA], [http://www.ebi.ac.uk/pdbsum/1fdp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fdp RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Azoospermia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=400005 400005]], Complement factor D deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134350 134350]], Corneal fleck dystrophy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609414 609414]], Properdin deficiency, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300383 300383]] | ||
==About this Structure== | ==About this Structure== | ||
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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 Sun Mar 30 20:20:54 2008'' |
Revision as of 17:20, 30 March 2008
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| , resolution 2.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , and | ||||||
| Activity: | Complement factor D, with EC number 3.4.21.46 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PROENZYME OF HUMAN COMPLEMENT FACTOR D, RECOMBINANT PROFACTOR D
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.
About this Structure
1FDP is a Single protein structure of sequence from Homo sapiens. 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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