View source for 4y40


==Structure of Vaspin mutant D305C V383C==
<StructureSection load='4y40' size='340' side='right'caption='[[4y40]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4y40]] 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=4Y40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y40 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <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=4y40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y40 OCA], [https://pdbe.org/4y40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y40 RCSB], [https://www.ebi.ac.uk/pdbsum/4y40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y40 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPA12_HUMAN SPA12_HUMAN] May modulate insulin action conceivably only in the presence of its yet undefined target proteases in white adipose tissues.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SerpinA12 (vaspin) is thought to be mainly expressed in adipose tissue and has multiple beneficial effects on metabolic, inflammatory and atherogenic processes related to obesity. Kallikrein 7 (KLK7) is the only known protease target of vaspin to date and is inhibited with a moderate inhibition rate. In the crystal structure, the cleavage site (P1-P1') of the vaspin reactive center loop is fairly rigid compared to the flexible residues before P2, possibly supported by an ionic interaction of P1' glutamate (Glu379) with an arginine residue (Arg302) of the beta-sheet C. A P1' glutamate seems highly unusual and unfavorable for the protease KLK7. We characterized vaspin mutants to investigate the roles of these two residues in protease inhibition and recognition by vaspin. RCL mutations changing the P1' residue or altering RCL conformation significantly increased inhibition parameters while removal of the positive charge within beta-sheet C impeded the serpin-protease interaction. Arg302 is a crucial contact to enable vaspin recognition by KLK7 and it supports moderate inhibition of the serpin despite the presence of the detrimental P1' Glu379, which clearly represents a major limiting factor for vaspin inhibitory activity. We also show that the vaspin inhibition rate for KLK7 can be modestly increased by heparin and demonstrate that vaspin is a heparin-binding serpin. Noteworthy, we observed vaspin as a remarkably thermostable serpin and found residues Glu379 and Arg302 influencing heat-induced polymerization. These structural and functional results reveal the mechanistic basis of how reactive center loop sequence and exosite interaction in vaspin enable KLK7 recognition and regulate protease inhibition as well as stability of this adipose tissue derived serpin.

A unique serpin P1' glutamate and a conserved beta-sheet C arginine are key residues for activity, protease recognition and stability of serpinA12 (vaspin).,Ulbricht D, Pippel J, Schultz S, Meier R, Strater N, Heiker JT Biochem J. 2015 Jul 21. pii: BJ20150643. PMID:26199422<ref>PMID:26199422</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4y40" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serpin 3D structures|Serpin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Heiker JT]]
[[Category: Meier R]]
[[Category: Pippel J]]
[[Category: Schultz S]]
[[Category: Strater N]]
[[Category: Ulbricht D]]