4ga7: Difference between revisions
No edit summary |
No edit summary |
||
| (5 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Crystal structure of human serpinB1 mutant== | |||
<StructureSection load='4ga7' size='340' side='right'caption='[[4ga7]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ga7]] is a 2 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=4GA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GA7 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]] 2.9Å</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=4ga7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ga7 OCA], [https://pdbe.org/4ga7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ga7 RCSB], [https://www.ebi.ac.uk/pdbsum/4ga7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ga7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ILEU_HUMAN ILEU_HUMAN] Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3. Also functions as a potent intracellular inhibitor of granzyme H.<ref>PMID:11747453</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The granzyme/perforin pathway is a major mechanism for cytotoxic lymphocytes to eliminate virus-infected and tumor cells. The balance between activation and inhibition of the proteolytic cascade must be tightly controlled to avoid self damage. Granzyme H (GzmH) is constitutively expressed in NK cells and induces target cell death; however, how GzmH activity is regulated remains elusive. We reported earlier the crystal structures of inactive D102N-GzmH alone and in complex with its synthetic substrate and inhibitor, as well as defined the mechanisms of substrate recognition and enzymatic activation. In this study, we identified SERPINB1 as a potent intracellular inhibitor for GzmH. Upon cleavage of the reactive center loop at Phe(343), SERPINB1 forms an SDS-stable covalent complex with GzmH. SERPINB1 overexpression suppresses GzmH- or LAK cell-mediated cytotoxicity. We determined the crystal structures of active GzmH and SERPINB1 (LM-DD mutant) in the native conformation to 3.0- and 2.9-A resolution, respectively. Molecular modeling reveals the possible conformational changes in GzmH for the suicide inhibition. Our findings provide new insights into the inhibitory mechanism of SERPINB1 against human GzmH. | |||
Identification of SERPINB1 As a Physiological Inhibitor of Human Granzyme H.,Wang L, Li Q, Wu L, Liu S, Zhang Y, Yang X, Zhu P, Zhang H, Zhang K, Lou J, Liu P, Tong L, Sun F, Fan Z J Immunol. 2012 Dec 26. PMID:23269243<ref>PMID:23269243</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ga7" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Serpin 3D structures|Serpin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Fan | [[Category: Large Structures]] | ||
[[Category: Li | [[Category: Fan Z]] | ||
[[Category: Sun | [[Category: Li Q]] | ||
[[Category: Tong | [[Category: Sun F]] | ||
[[Category: Wang | [[Category: Tong L]] | ||
[[Category: Wu | [[Category: Wang L]] | ||
[[Category: Zhang | [[Category: Wu L]] | ||
[[Category: Zhang K]] | |||