2crd

From Proteopedia

(Difference between revisions)

Current revision

ANALYSIS OF SIDE-CHAIN ORGANIZATION ON A REFINED MODEL OF CHARYBDOTOXIN: STRUCTURAL AND FUNCTIONAL IMPLICATIONS

Structural highlights

2crd is a 1 chain structure with sequence from Leiurus hebraeus. The February 2003 RCSB PDB Molecule of the Month feature on Potassium Channels by Shuchismita Dutta and David S. Goodsell is 10.2210/rcsb_pdb/mom_2003_2. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 12 models
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAX11_LEIHE This toxin inhibits numerous potassium channels: shaker (Ki=227 nM), Kv1.2/KCNA2 (nanomolar range), Kv1.3/KCNA3 (nanomolar range), Kv1.5/KCNA5 (Kd>100 nM), Kv1.6/KCNA6 (Ki=22 nM), KCa1.1/KCNMA1 (IC(50)=5.9 nM). It blocks channel activity by a simple bimolecular inhibition process. It also shows a weak interaction with nicotinic acetylcholine receptors (nAChR), suggesting it may weakly inhibit it (PubMed:31276191). It also exhibits pH-specific antimicrobial activities against bacteria (B.subtilis, E.coli and S.aureus) and the fungus C.albicans (PubMed:15118082).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The spatial organization of side chains on a refined model of charybdotoxin is presented. First, the structural role of two groups of well-defined, low-accessible side chains (Thr3, Val5, Val16, Leu20, Cys33 and Leu20, His21, Thr23, Cys17, Cys35) is discussed. These side chains are conserved in three out of the five known scorpion toxins acting on K+ channels. Interestingly, they are not conserved in scyllatoxin which presents a slightly different secondary structure organization. Second, the spatial organization of all positively charged residues is analyzed. Comparison with the results presented by Park and Miller [(1992) Biochemistry (preceding paper in this issue)] shows that all functionally important positive residues are located on the beta-sheet side of the toxin. These results are different from those obtained by Auguste et al. [(1992) Biochemistry 31, 648-654] on scyllatoxin, which blocks a different type of K+ channel. This study shows, in fact, that functionally important positive residues are located on the helix side of the toxin. Thus, charybdotoxin and scyllatoxin, which present the same global fold, interact with two different classes of K+ channels by two different parts of the motif.

Analysis of side-chain organization on a refined model of charybdotoxin: structural and functional implications.,Bontems F, Gilquin B, Roumestand C, Menez A, Toma F Biochemistry. 1992 Sep 1;31(34):7756-64. PMID:1380828^[8]

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

References

↑ Castle NA, London DO, Creech C, Fajloun Z, Stocker JW, Sabatier JM. Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Mol Pharmacol. 2003 Feb;63(2):409-18. PMID:12527813
↑ Yount NY, Yeaman MR. Multidimensional signatures in antimicrobial peptides. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7363-8. Epub 2004 Apr 26. PMID:15118082 doi:10.1073/pnas.0401567101
↑ Takacs Z, Toups M, Kollewe A, Johnson E, Cuello LG, Driessens G, Biancalana M, Koide A, Ponte CG, Perozo E, Gajewski TF, Suarez-Kurtz G, Koide S, Goldstein SA. A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library. Proc Natl Acad Sci U S A. 2009 Dec 10. PMID:20007782
↑ Lucchesi K, Ravindran A, Young H, Moczydlowski E. Analysis of the blocking activity of charybdotoxin homologs and iodinated derivatives against Ca2+-activated K+ channels. J Membr Biol. 1989 Aug;109(3):269-81. PMID:2477548 doi:10.1007/BF01870284
↑ Kasheverov IE, Oparin PB, Zhmak MN, Egorova NS, Ivanov IA, Gigolaev AM, Nekrasova OV, Serebryakova MV, Kudryavtsev DS, Prokopev NA, Hoang AN, Tsetlin VI, Vassilevski AA, Utkin YN. Scorpion toxins interact with nicotinic acetylcholine receptors. FEBS Lett. 2019 Oct;593(19):2779-2789. PMID:31276191 doi:10.1002/1873-3468.13530
↑ Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227-34 PMID:7517498
↑ Garcia ML, Garcia-Calvo M, Hidalgo P, Lee A, MacKinnon R. Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochemistry. 1994 Jun 7;33(22):6834-9. PMID:8204618 doi:10.1021/bi00188a012
↑ Bontems F, Gilquin B, Roumestand C, Menez A, Toma F. Analysis of side-chain organization on a refined model of charybdotoxin: structural and functional implications. Biochemistry. 1992 Sep 1;31(34):7756-64. PMID:1380828

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='2crd' size='340' side='right'caption='[[2crd]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2crd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_quinquestriatus_hebraeus Leiurus quinquestriatus hebraeus]. The February 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Potassium Channels''  by Shuchismita Dutta and David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_2 10.2210/rcsb_pdb/mom_2003_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CRD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2crd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_hebraeus Leiurus hebraeus]. The February 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Potassium Channels''  by Shuchismita Dutta and David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_2 10.2210/rcsb_pdb/mom_2003_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CRD 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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 12 models</td></tr>
 <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=2crd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2crd OCA], [https://pdbe.org/2crd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2crd RCSB], [https://www.ebi.ac.uk/pdbsum/2crd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2crd ProSAT]</span></td></tr>
@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cr/2crd_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Leiurus quinquestriatus hebraeus]]
+[[Category: Leiurus hebraeus]]
 [[Category: Potassium Channels]]
 [[Category: RCSB PDB Molecule of the Month]]

2crd

From Proteopedia

Current revision

ANALYSIS OF SIDE-CHAIN ORGANIZATION ON A REFINED MODEL OF CHARYBDOTOXIN: STRUCTURAL AND FUNCTIONAL IMPLICATIONS

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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