1dst
From Proteopedia
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|SITE= | |SITE= | ||
|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=1dst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dst OCA], [http://www.ebi.ac.uk/pdbsum/1dst PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dst RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Complement factor D is a serine protease regulated by a novel mechanism that depends on conformational changes rather than cleavage of a zymogen for expression of proteolytic activity. The conformational changes are presumed to be induced by the single natural substrate, C3bB, and to result in reversible reorientation of the catalytic center and of the substrate binding site of factor D, both of which have atypical conformations. Here we report that replacement of Ser94, Thr214, and Ser215 of factor D (chymotrypsinogen numbering has been used for comparison purposes) with the corresponding residues of trypsin, Tyr, Ser, and Trp, is sufficient to induce substantially higher catalytic activity associated with a typical serine protease alignment of the catalytic triad residues His57, Asp102, and Ser195. These results provide a partial structural explanation for the low reactivity of "resting-state" factor D toward synthetic substrates. | Complement factor D is a serine protease regulated by a novel mechanism that depends on conformational changes rather than cleavage of a zymogen for expression of proteolytic activity. The conformational changes are presumed to be induced by the single natural substrate, C3bB, and to result in reversible reorientation of the catalytic center and of the substrate binding site of factor D, both of which have atypical conformations. Here we report that replacement of Ser94, Thr214, and Ser215 of factor D (chymotrypsinogen numbering has been used for comparison purposes) with the corresponding residues of trypsin, Tyr, Ser, and Trp, is sufficient to induce substantially higher catalytic activity associated with a typical serine protease alignment of the catalytic triad residues His57, Asp102, and Ser195. These results provide a partial structural explanation for the low reactivity of "resting-state" factor D toward synthetic substrates. | ||
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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: serine protease]] | [[Category: serine protease]] | ||
| - | ''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 19:47:58 2008'' |
Revision as of 16:48, 30 March 2008
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| , resolution 2.0Å | |||||||
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| Activity: | Complement factor D, with EC number 3.4.21.46 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
MUTANT OF FACTOR D WITH ENHANCED CATALYTIC ACTIVITY
Overview
Complement factor D is a serine protease regulated by a novel mechanism that depends on conformational changes rather than cleavage of a zymogen for expression of proteolytic activity. The conformational changes are presumed to be induced by the single natural substrate, C3bB, and to result in reversible reorientation of the catalytic center and of the substrate binding site of factor D, both of which have atypical conformations. Here we report that replacement of Ser94, Thr214, and Ser215 of factor D (chymotrypsinogen numbering has been used for comparison purposes) with the corresponding residues of trypsin, Tyr, Ser, and Trp, is sufficient to induce substantially higher catalytic activity associated with a typical serine protease alignment of the catalytic triad residues His57, Asp102, and Ser195. These results provide a partial structural explanation for the low reactivity of "resting-state" factor D toward synthetic substrates.
About this Structure
1DST is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of a complement factor D mutant expressing enhanced catalytic activity., Kim S, Narayana SV, Volanakis JE, J Biol Chem. 1995 Oct 13;270(41):24399-405. PMID:7592653
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