This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2n71

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 18:30, 27 July 2022

NMR structure of CmPI-II, a serin protease inhibitor isolated from mollusk Cenchitis muricatus

Structural highlights

2n71 is a 1 chain structure with sequence from Beaded periwinkle. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IPK2_CENMR] Serine protease inhibitor. Strongly inhibits human neutrophil elastase and trypsin, also inhibits porcine pancreatic elastase and subtilisin A. Does not inhibit chymotrypsin, plasma kallikrein, pancreatic kallikrein, thrombin or papain.^[1] ^[2]

Publication Abstract from PubMed

Subtilisin-like proteases play crucial roles in host-pathogen interactions. Thus, protease inhibitors constitute important tools in the regulation of this interaction. CmPI-II is a Kazal proteinase inhibitor isolated from Cenchritis muricatus that inhibits subtilisin A, trypsin and elastases. Based on sequence analysis it defines a new group of non-classical Kazal inhibitors. Lacking solved 3D structures from this group prevents the straightforward structural comparison with other Kazal inhibitors. The 3D structure of CmPI-II, solved in this work using NMR techniques, shows the typical fold of Kazal inhibitors, but has significant differences in its N-terminal moiety, the disposition of the CysI-CysV disulfide bond and the reactive site loop (RSL) conformation. The high flexibility of its N-terminal region, the RSL, and the alpha-helix observed in NMR experiments and molecular dynamics simulations, suggest a coupled motion of these regions that could explain CmPI-II broad specificity. The 3D structure of the CmPI-II/subtilisin A complex, obtained by modeling, allows understanding of the energetic basis of the subtilisin A inhibition. The residues at the P2 and P2' positions of the inhibitor RSL were predicted to be major contributors to the binding free energy of the complex, rather than those at the P1 position. Site directed mutagenesis experiments confirmed the Trp14 (P2') contribution to CmPI-II/subtilisin A complex formation. Overall, this work provides the structural determinants for the subtilisin A inhibition by CmPI-II and allows the designing of more specific and potent molecules. In addition, the 3D structure obtained supports the existence of a new group in non-classical Kazal inhibitors.

NMR structure of CmPI-II, a non-classical Kazal protease inhibitor: Understanding its conformational dynamics and subtilisin A inhibition.,Cabrera-Munoz A, Valiente PA, Rojas L, Alonso-Del-Rivero Antigua M, Pires JR J Struct Biol. 2019 Jun 1;206(3):280-294. doi: 10.1016/j.jsb.2019.03.011. Epub, 2019 Mar 28. PMID:30930219^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gonzalez Y, Tanaka AS, Hirata IY, del Rivero MA, Oliva ML, Araujo MS, Chavez MA. Purification and partial characterization of human neutrophil elastase inhibitors from the marine snail Cenchritis muricatus (Mollusca). Comp Biochem Physiol A Mol Integr Physiol. 2007 Apr;146(4):506-13. Epub 2006 Mar , 20. PMID:16546427 doi:http://dx.doi.org/10.1016/j.cbpa.2006.01.022
↑ Gonzalez Y, Pons T, Gil J, Besada V, Alonso-del-Rivero M, Tanaka AS, Araujo MS, Chavez MA. Characterization and comparative 3D modeling of CmPI-II, a novel 'non-classical' Kazal-type inhibitor from the marine snail Cenchritis muricatus (Mollusca). Biol Chem. 2007 Nov;388(11):1183-94. PMID:17976011 doi:http://dx.doi.org/10.1515/BC.2007.129
↑ Cabrera-Munoz A, Valiente PA, Rojas L, Alonso-Del-Rivero Antigua M, Pires JR. NMR structure of CmPI-II, a non-classical Kazal protease inhibitor: Understanding its conformational dynamics and subtilisin A inhibition. J Struct Biol. 2019 Jun 1;206(3):280-294. doi: 10.1016/j.jsb.2019.03.011. Epub, 2019 Mar 28. PMID:30930219 doi:http://dx.doi.org/10.1016/j.jsb.2019.03.011

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n71"

@@ Line 3: / Line 3: @@
 <StructureSection load='2n71' size='340' side='right'caption='[[2n71]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n71]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Beaded_periwinkle Beaded periwinkle]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N71 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2N71 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n71]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Beaded_periwinkle Beaded periwinkle]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N71 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2n71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n71 OCA], [http://pdbe.org/2n71 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n71 RCSB], [http://www.ebi.ac.uk/pdbsum/2n71 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n71 ProSAT]</span></td></tr>
+</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=2n71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n71 OCA], [https://pdbe.org/2n71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n71 RCSB], [https://www.ebi.ac.uk/pdbsum/2n71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n71 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/IPK2_CENMR IPK2_CENMR]] Serine protease inhibitor. Strongly inhibits human neutrophil elastase and trypsin, also inhibits porcine pancreatic elastase and subtilisin A. Does not inhibit chymotrypsin, plasma kallikrein, pancreatic kallikrein, thrombin or papain.<ref>PMID:16546427</ref> <ref>PMID:17976011</ref>
+[[https://www.uniprot.org/uniprot/IPK2_CENMR IPK2_CENMR]] Serine protease inhibitor. Strongly inhibits human neutrophil elastase and trypsin, also inhibits porcine pancreatic elastase and subtilisin A. Does not inhibit chymotrypsin, plasma kallikrein, pancreatic kallikrein, thrombin or papain.<ref>PMID:16546427</ref> <ref>PMID:17976011</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2n71

From Proteopedia

Revision as of 18:30, 27 July 2022

NMR structure of CmPI-II, a serin protease inhibitor isolated from mollusk Cenchitis muricatus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox