View source for 3tjv


==Crystal structure of human granzyme H with a peptidyl substrate==
<StructureSection load='3tjv' size='340' side='right'caption='[[3tjv]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tjv]] 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=3TJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJV 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]] 2.4&#8491;</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=3tjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tjv OCA], [https://pdbe.org/3tjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tjv RCSB], [https://www.ebi.ac.uk/pdbsum/3tjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tjv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRAH_HUMAN GRAH_HUMAN] Cytotoxic chymotrypsin-like serine protease with preference for bulky and aromatic residues at the P1 position and acidic residues at the P3' and P4' sites. Probably necessary for target cell lysis in cell-mediated immune responses. Participates in the antiviral response via direct cleavage of several proteins essential for viral replication.<ref>PMID:22156497</ref> <ref>PMID:23269243</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human granzyme H (GzmH) is constitutively expressed in human NK cells that have important roles in innate immune responses against tumors and viruses. GzmH is a chymotrypsin-like serine protease. Its substrate preference and its mechanism of substrate recognition are poorly understood. To provide structural insights into the substrate recognition mechanisms for GzmH, we solved the crystal structures of a D102N-GzmH mutant alone and in complex with a decapeptide substrate and an inhibitor to 2.2 A, 2.4 A, and 2.7 A, respectively. The Thr(189), Gly(216), and Gly(226) specificity triad in the S1 pocket of GzmH defines its preference for bulky, aromatic residues (Tyr and Phe) at the P1 position. Notably, we discovered that an unusual RKR motif (Arg(39)-Lys(40)-Arg(41)), conserved only in GzmH, helps define the S3' and S4' binding regions, indicating the preference for acidic residues at the P3' and P4' sites. Disruption of the RKR motif or the acidic P3' and P4' residues in the substrate abolished the proteolytic activity of GzmH. We designed a tetrapeptide chloromethylketone inhibitor, Ac-PTSY-chloromethylketone, which can selectively and efficiently block the enzymatic and cytotoxic activity of GzmH, providing a useful tool for further studies on the function of GzmH.

Structural Insights into the Substrate Specificity of Human Granzyme H: The Functional Roles of a Novel RKR Motif.,Wang L, Zhang K, Wu L, Liu S, Zhang H, Zhou Q, Tong L, Sun F, Fan Z J Immunol. 2011 Dec 9. PMID:22156497<ref>PMID:22156497</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3tjv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Granzyme|Granzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fan Z]]
[[Category: Sun F]]
[[Category: Tong L]]
[[Category: Wang L]]
[[Category: Wu L]]
[[Category: Zhang K]]