View source for 4roa


==1.90A resolution structure of SRPN2 (S358W) from Anopheles gambiae==
<StructureSection load='4roa' size='340' side='right'caption='[[4roa]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4roa]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anopheles_gambiae Anopheles gambiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ROA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ROA 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]] 1.9&#8491;</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=4roa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4roa OCA], [https://pdbe.org/4roa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4roa RCSB], [https://www.ebi.ac.uk/pdbsum/4roa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4roa ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SP2_ANOGA SP2_ANOGA] Serine protease inhibitor that functions in the melanization-mediated immune response (PubMed:16113656, PubMed:20953892, PubMed:33520733, PubMed:33045027, PubMed:21465556, PubMed:25525260). By preventing the activation of phenoloxidases through the inhibiting of serine proteases CLIPB9 and CLIPB10, negatively regulates melanization in the hemolymph (PubMed:16113656, PubMed:20953892, PubMed:33520733, PubMed:33045027, PubMed:21465556, PubMed:25525260). By preventing melanization, has a detrimental role during P.berghei parasite mediated-infection and invasion of the mosquito midgut (PubMed:16113656).<ref>PMID:16113656</ref> <ref>PMID:20953892</ref> <ref>PMID:21465556</ref> <ref>PMID:25525260</ref> <ref>PMID:33045027</ref> <ref>PMID:33520733</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serpin-2 (SRPN2) is a key negative regulator of the melanization response in the malaria vector Anopheles gambiae. SRPN2 irreversibly inhibits clip domain serine proteinase 9 (CLIPB9), which functions in a serine proteinase cascade culminating in the activation of prophenoloxidase and melanization. Silencing of SRPN2 in A. gambiae results in spontaneous melanization and decreased life span and is therefore a promising target for vector control. The previously determined structure of SRPN2 revealed a partial insertion of the hinge region of the reactive center loop (RCL) into beta sheet A. This partial hinge insertion participates in heparin-linked activation in other serpins, notably antithrombin III. SRPN2 does not contain a heparin binding site, and any possible mechanistic function of the hinge insertion was previously unknown. To investigate the function of the SRPN2 hinge insertion, we developed three SRPN2 variants in which the hinge regions are either constitutively expelled or inserted and analyzed their structure, thermostability, and inhibitory activity. We determined that constitutive hinge expulsion resulted in a 2.7-fold increase in the rate of CLIPB9Xa inhibition, which is significantly lower than previous observations of allosteric serpin activation. Furthermore, we determined that stable insertion of the hinge region did not appreciably decrease the accessibility of the RCL to CLIPB9. Together, these results indicate that the partial hinge insertion in SRPN2 does not participate in the allosteric activation observed in other serpins and instead represents a molecular trade-off between RCL accessibility and efficient formation of an inhibitory complex with the cognate proteinase.

Structural and Inhibitory Effects of Hinge Loop Mutagenesis in Serpin-2 from the Malaria Vector Anopheles gambiae.,Zhang X, Meekins DA, An C, Zolkiewski M, Battaile KP, Kanost MR, Lovell S, Michel K J Biol Chem. 2015 Jan 30;290(5):2946-56. doi: 10.1074/jbc.M114.625665. Epub 2014 , Dec 17. PMID:25525260<ref>PMID:25525260</ref>

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

==See Also==
*[[Serpin 3D structures|Serpin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Anopheles gambiae]]
[[Category: Large Structures]]
[[Category: An C]]
[[Category: Battaile KP]]
[[Category: Lovell S]]
[[Category: Meekins DA]]
[[Category: Michel K]]
[[Category: Zhang X]]