1dst
From Proteopedia
(New page: 200px<br /> <applet load="1dst" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dst, resolution 2.0Å" /> '''MUTANT OF FACTOR D W...) |
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| - | [[Image:1dst.gif|left|200px]]<br /> | + | [[Image:1dst.gif|left|200px]]<br /><applet load="1dst" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dst" size=" | + | |
caption="1dst, resolution 2.0Å" /> | caption="1dst, resolution 2.0Å" /> | ||
'''MUTANT OF FACTOR D WITH ENHANCED CATALYTIC ACTIVITY'''<br /> | '''MUTANT OF FACTOR D WITH ENHANCED CATALYTIC ACTIVITY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Complement factor D is a serine protease regulated by a novel mechanism | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DST is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http:// | + | 1DST is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DST OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Narayana, S | + | [[Category: Narayana, S V.L.]] |
| - | [[Category: Volanakis, J | + | [[Category: Volanakis, J E.]] |
[[Category: complement activating enzyme]] | [[Category: complement activating enzyme]] | ||
[[Category: factor d]] | [[Category: factor d]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:20:07 2008'' |
Revision as of 10:20, 21 February 2008
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MUTANT OF FACTOR D WITH ENHANCED CATALYTIC ACTIVITY
Contents |
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.
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
1DST is a Single protein structure of sequence from Homo sapiens. Active as Complement factor D, with EC number 3.4.21.46 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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