3fzz: Difference between revisions
No edit summary |
No edit summary |
||
| (8 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of GrC== | |||
<StructureSection load='3fzz' size='340' side='right'caption='[[3fzz]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3fzz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FZZ FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3fzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fzz OCA], [https://pdbe.org/3fzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fzz RCSB], [https://www.ebi.ac.uk/pdbsum/3fzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fzz ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GRAC_MOUSE GRAC_MOUSE] This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fz/3fzz_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fzz ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Proteases act in important homeostatic pathways and are tightly regulated. Here, we report an unusual structural mechanism of regulation observed by the 2.5-A X-ray crystal structure of the serine protease, granzyme C. Although the active-site triad residues adopt canonical conformations, the oxyanion hole is improperly formed, and access to the primary specificity (S1) pocket is blocked through a reversible rearrangement involving Phe-191. Specifically, a register shift in the 190-strand preceding the active-site serine leads to Phe-191 filling the S1 pocket. Mutation of a unique Glu-Glu motif at positions 192-193 unlocks the enzyme, which displays chymase activity, and proteomic analysis confirms that activity of the wild-type protease can be released through interactions with an appropriate substrate. The 2.5-A structure of the unlocked enzyme reveals unprecedented flexibility in the 190-strand preceding the active-site serine that results in Phe-191 vacating the S1 pocket. Overall, these observations describe a broadly applicable mechanism of protease regulation that cannot be predicted by template-based modeling or bioinformatic approaches alone. | |||
Structure of granzyme C reveals an unusual mechanism of protease autoinhibition.,Kaiserman D, Buckle AM, Van Damme P, Irving JA, Law RH, Matthews AY, Bashtannyk-Puhalovich T, Langendorf C, Thompson P, Vandekerckhove J, Gevaert K, Whisstock JC, Bird PI Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5587-92. Epub 2009 Mar 19. PMID:19299505<ref>PMID:19299505</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3fzz" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Granzyme|Granzyme]] | *[[Granzyme|Granzyme]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Buckle | [[Category: Buckle AM]] | ||
[[Category: Kaiserman | [[Category: Kaiserman D]] | ||
[[Category: Whisstock | [[Category: Whisstock JC]] | ||
Latest revision as of 12:10, 30 October 2024
Structure of GrCStructure of GrC
Structural highlights
FunctionGRAC_MOUSE This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedProteases act in important homeostatic pathways and are tightly regulated. Here, we report an unusual structural mechanism of regulation observed by the 2.5-A X-ray crystal structure of the serine protease, granzyme C. Although the active-site triad residues adopt canonical conformations, the oxyanion hole is improperly formed, and access to the primary specificity (S1) pocket is blocked through a reversible rearrangement involving Phe-191. Specifically, a register shift in the 190-strand preceding the active-site serine leads to Phe-191 filling the S1 pocket. Mutation of a unique Glu-Glu motif at positions 192-193 unlocks the enzyme, which displays chymase activity, and proteomic analysis confirms that activity of the wild-type protease can be released through interactions with an appropriate substrate. The 2.5-A structure of the unlocked enzyme reveals unprecedented flexibility in the 190-strand preceding the active-site serine that results in Phe-191 vacating the S1 pocket. Overall, these observations describe a broadly applicable mechanism of protease regulation that cannot be predicted by template-based modeling or bioinformatic approaches alone. Structure of granzyme C reveals an unusual mechanism of protease autoinhibition.,Kaiserman D, Buckle AM, Van Damme P, Irving JA, Law RH, Matthews AY, Bashtannyk-Puhalovich T, Langendorf C, Thompson P, Vandekerckhove J, Gevaert K, Whisstock JC, Bird PI Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5587-92. Epub 2009 Mar 19. PMID:19299505[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||