View source for 2kxg


==The solution structure of the squash aspartic acid proteinase inhibitor (SQAPI)==
<StructureSection load='2kxg' size='340' side='right'caption='[[2kxg]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kxg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cucurbita_maxima Cucurbita maxima]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KXG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kxg OCA], [https://pdbe.org/2kxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kxg RCSB], [https://www.ebi.ac.uk/pdbsum/2kxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kxg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6DLC9_CUCMA Q6DLC9_CUCMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The squash aspartic acid proteinase inhibitor (SQAPI), a proteinaceous proteinase inhibitor from squash, is an effective inhibitor of a range of aspartic proteinases. Proteinaceous aspartic proteinase inhibitors are rare in nature. The only other example in plants probably evolved from a precursor serine proteinase inhibitor. Earlier work based on sequence homology modeling suggested SQAPI evolved from an ancestral cystatin. In this work, we determined the solution structure of SQAPI using NMR and show that SQAPI shares the same fold as a plant cystatin. The structure is characterized by a four-strand anti-parallel beta-sheet gripping an alpha-helix in an analogous manner to fingers of a hand gripping a tennis racquet. Truncation and site-specific mutagenesis revealed that the unstructured N terminus and the loop connecting beta-strands 1 and 2 are important for pepsin inhibition, but the loop connecting strands 3 and 4 is not. Using ambiguous restraints based on the mutagenesis results, SQAPI was then docked computationally to pepsin. The resulting model places the N-terminal strand of SQAPI in the S' side of the substrate binding cleft, whereas the first SQAPI loop binds on the S side of the cleft. The backbone of SQAPI does not interact with the pepsin catalytic Asp(32)-Asp(215) diad, thus avoiding cleavage. The data show that SQAPI does share homologous structural elements with cystatin and appears to retain a similar protease inhibitory mechanism despite its different target. This strongly supports our hypothesis that SQAPI evolved from an ancestral cystatin.

Solution structure of the squash aspartic acid proteinase inhibitor (SQAPI) and mutational analysis of pepsin inhibition.,Headey SJ, Macaskill UK, Wright MA, Claridge JK, Edwards PJ, Farley PC, Christeller JT, Laing WA, Pascal SM J Biol Chem. 2010 Aug 27;285(35):27019-25. Epub 2010 Jun 9. PMID:20538608<ref>PMID:20538608</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2kxg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cucurbita maxima]]
[[Category: Large Structures]]
[[Category: Christeller JT]]
[[Category: Claridge JK]]
[[Category: Edwards PJB]]
[[Category: Farley PC]]
[[Category: Headey SJ]]
[[Category: Laing WA]]
[[Category: Macaskill UK]]
[[Category: Pascal SM]]
[[Category: Wright M]]