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| <StructureSection load='1op8' size='340' side='right'caption='[[1op8]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='1op8' size='340' side='right'caption='[[1op8]], [[Resolution|resolution]] 2.50Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[1op8]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OP8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OP8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1op8]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OP8 FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Granzyme_A Granzyme A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.78 3.4.21.78] </span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1op8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1op8 OCA], [http://pdbe.org/1op8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1op8 RCSB], [http://www.ebi.ac.uk/pdbsum/1op8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1op8 ProSAT]</span></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=1op8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1op8 OCA], [https://pdbe.org/1op8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1op8 RCSB], [https://www.ebi.ac.uk/pdbsum/1op8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1op8 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/GRAA_HUMAN GRAA_HUMAN]] This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.<ref>PMID:12524539</ref> | + | [https://www.uniprot.org/uniprot/GRAA_HUMAN GRAA_HUMAN] This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.<ref>PMID:12524539</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| <jmolCheckbox> | | <jmolCheckbox> |
| <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/op/1op8_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/op/1op8_consurf.spt"</scriptWhenChecked> |
- | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| </jmolCheckbox> | | </jmolCheckbox> |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Granzyme A]] | + | [[Category: Homo sapiens]] |
- | [[Category: Human]]
| + | |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Bode, W]] | + | [[Category: Bode W]] |
- | [[Category: Estebanez-Perpina, E]] | + | [[Category: Estebanez-Perpina E]] |
- | [[Category: Hink-Schauer, C]] | + | [[Category: Hink-Schauer C]] |
- | [[Category: Jenne, D]] | + | [[Category: Jenne D]] |
- | [[Category: Apoptosis]]
| + | |
- | [[Category: Granzyme some]]
| + | |
- | [[Category: Hydrolase]]
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- | [[Category: Serine proteinase]]
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| Structural highlights
Function
GRAA_HUMAN This enzyme is necessary for target cell lysis in cell-mediated immune responses. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Involved in apoptosis.[1]
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 PubMed
Granzyme A (GzmA) belongs to a family of trypsin-like serine proteases localized in cytoplasmic granules of activated lymphocytes and natural killer (NK) cells. In contrast to the related granzyme B (GzmB), GzmA forms a stable disulfide-linked homodimer and triggers target-cell death in a caspase-independent way. Limited proteolysis of a high-molecular-mass complex containing SET (also named putative HLA-associated protein II or PHAPII), PHAPI (pp32, leucine-rich acidic nuclear protein) and HMG2 by GzmA liberates NM23-H1, a Mg2+-dependent DNase that causes single-stranded breaks in nuclear DNA. By analyzing the dimeric GzmA structure at a resolution of 2.5 A, we determined the substrate-binding constraints and selective advantages of the two domains arranged as a unique functional tandem. The active sites of the two subunits point in opposite directions and the nearby noncatalytic surfaces can function as exosites, presenting substrates to the active site region of the adjacent partner in a manner analogous to staphylokinase or streptokinase, which present plasminogen to the cofactor-plasmin and cofactor-plasminogen complexes.
Crystal structure of the apoptosis-inducing human granzyme A dimer.,Hink-Schauer C, Estebanez-Perpina E, Kurschus FC, Bode W, Jenne DE Nat Struct Biol. 2003 Jul;10(7):535-40. PMID:12819770[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fan Z, Beresford PJ, Zhang D, Xu Z, Novina CD, Yoshida A, Pommier Y, Lieberman J. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003 Feb;4(2):145-53. Epub 2003 Jan 13. PMID:12524539 doi:10.1038/ni885
- ↑ Hink-Schauer C, Estebanez-Perpina E, Kurschus FC, Bode W, Jenne DE. Crystal structure of the apoptosis-inducing human granzyme A dimer. Nat Struct Biol. 2003 Jul;10(7):535-40. PMID:12819770 doi:10.1038/nsb945
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