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3mz8

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Crystal Structure of Zinc-Bound Natrin From Naja atra

Structural highlights

3mz8 is a 2 chain structure with sequence from Naja atra. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CRVP1_NAJAT Inhibits calcium-activated potassium channels (KCa1.1/KCNMA1), voltage-gated potassium channel Kv1.3/KCNA3, and the calcium release channel/ryanodine receptor (RyR). Binds specifically to type 1 RyR (RyR1) from skeletal muscle. Inhibit both the binding of ryanodine to RyR1, and RyR1's calcium-channel activity. Inhibits carbachol-induced muscle contraction and weakly blocks muscle contraction evoked by potassium.^[1] ^[2] ^[3] ^[4]

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

Cysteine-rich secretory proteins (CRISPs) have been identified as a toxin family in most animal venoms with biological functions mainly associated with the ion channel activity of cysteine-rich domain (CRD). CRISPs also bind to Zn(2+) at their N-terminal pathogenesis-related (PR-1) domain, but their function remains unknown. Interestingly, similar Zn(2+)-binding site exists in all CRISP family, including those identified in a wide range of organisms. Here, we report that the CRISP from Naja atra (natrin) could induce expression of vascular endothelial cell (EC) adhesion molecules, i.e., intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin, to promote monocytic cell adhesion in a heparan sulfate (HS)- and Zn(2+)-dependent manner. Using specific inhibitors and small interfering RNAs, the activation mechanisms are shown to involve both mitogen-activated protein kinases and nuclear factor-kappaB. Biophysical characterization of natrin by using fluorescence, circular-dichroism, and X-ray crystallographic methods further reveals the presence of two Zn(2+)-binding sites for natrin. The strong binding site is located near the putative Ser-His-Glu catalytic triad of the N-terminal domain. The weak binding site remains to be characterized, but it may modulate HS binding by enhancing its interaction with long chain HS. Our results strongly suggest that natrin may serve as an inflammatory modulator that could perturb wound-healing process of the bitten victim by regulating adhesion molecule expression in ECs. Our finding uncovers a new aspect of the biological role of CRISP family in immune response, and is expected to facilitate future development of new therapeutic strategy for the envenomed victims.

Cobra CRISP functions as an inflammatory modulator via a novel Zn2+- and heparan sulfate- dependent transcriptional regulation of endothelial cell adhesion molecules.,Wang YL, Kuo JH, Lee SC, Liu JS, Hsieh YC, Shih YT, Chen CJ, Chiu JJ, Wu WG J Biol Chem. 2010 Oct 2. PMID:20889969^[5]

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

References

↑ Chang LS, Liou JC, Lin SR, Cheng YC. Purification and characterization of Taiwan cobra venom proteins with weak toxicity. Toxicon. 2005 Jan;45(1):21-5. PMID:15581679 doi:10.1016/j.toxicon.2004.09.002
↑ Wang F, Li H, Liu MN, Song H, Han HM, Wang QL, Yin CC, Zhou YC, Qi Z, Shu YY, Lin ZJ, Jiang T. Structural and functional analysis of natrin, a venom protein that targets various ion channels. Biochem Biophys Res Commun. 2006 Dec 15;351(2):443-8. Epub 2006 Oct 20. PMID:17070778 doi:10.1016/j.bbrc.2006.10.067
↑ Zhou Q, Wang QL, Meng X, Shu Y, Jiang T, Wagenknecht T, Yin CC, Sui SF, Liu Z. Structural and functional characterization of ryanodine receptor-natrin toxin interaction. Biophys J. 2008 Nov 1;95(9):4289-99. doi: 10.1529/biophysj.108.137224. Epub 2008 , Jul 25. PMID:18658224 doi:10.1529/biophysj.108.137224
↑ Wang J, Shen B, Guo M, Lou X, Duan Y, Cheng XP, Teng M, Niu L, Liu Q, Huang Q, Hao Q. Blocking effect and crystal structure of natrin toxin, a cysteine-rich secretory protein from Naja atra venom that targets the BKCa channel. Biochemistry. 2005 Aug 2;44(30):10145-52. PMID:16042391 doi:10.1021/bi050614m
↑ Wang YL, Kuo JH, Lee SC, Liu JS, Hsieh YC, Shih YT, Chen CJ, Chiu JJ, Wu WG. Cobra CRISP functions as an inflammatory modulator via a novel Zn2+- and heparan sulfate- dependent transcriptional regulation of endothelial cell adhesion molecules. J Biol Chem. 2010 Oct 2. PMID:20889969 doi:10.1074/jbc.M110.146290

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3mz8"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Zinc-Bound Natrin From Naja atra==
-<StructureSection load='3mz8' size='340' side='right' caption='[[3mz8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='3mz8' size='340' side='right'caption='[[3mz8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3mz8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MZ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MZ8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3mz8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MZ8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xta|1xta]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3mz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mz8 OCA], [http://pdbe.org/3mz8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mz8 RCSB], [http://www.ebi.ac.uk/pdbsum/3mz8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mz8 ProSAT]</span></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=3mz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mz8 OCA], [https://pdbe.org/3mz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mz8 RCSB], [https://www.ebi.ac.uk/pdbsum/3mz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mz8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CRVP1_NAJAT CRVP1_NAJAT]] Inhibits calcium-activated potassium channels (KCa1.1/KCNMA1), voltage-gated potassium channel Kv1.3/KCNA3, and the calcium release channel/ryanodine receptor (RyR). Binds specifically to type 1 RyR (RyR1) from skeletal muscle. Inhibit both the binding of ryanodine to RyR1, and RyR1's calcium-channel activity. Inhibits carbachol-induced muscle contraction and weakly blocks muscle contraction evoked by potassium.<ref>PMID:15581679</ref> <ref>PMID:17070778</ref> <ref>PMID:18658224</ref> <ref>PMID:16042391</ref>
+[https://www.uniprot.org/uniprot/CRVP1_NAJAT CRVP1_NAJAT] Inhibits calcium-activated potassium channels (KCa1.1/KCNMA1), voltage-gated potassium channel Kv1.3/KCNA3, and the calcium release channel/ryanodine receptor (RyR). Binds specifically to type 1 RyR (RyR1) from skeletal muscle. Inhibit both the binding of ryanodine to RyR1, and RyR1's calcium-channel activity. Inhibits carbachol-induced muscle contraction and weakly blocks muscle contraction evoked by potassium.<ref>PMID:15581679</ref> <ref>PMID:17070778</ref> <ref>PMID:18658224</ref> <ref>PMID:16042391</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mz/3mz8_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mz/3mz8_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 33: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Naja atra]]
-[[Category: Chen, C J]]
+[[Category: Chen CJ]]
-[[Category: Hsieh, Y C]]
+[[Category: Hsieh YC]]
-[[Category: Liu, J S]]
+[[Category: Liu JS]]
-[[Category: Wang, Y L]]
+[[Category: Wang YL]]
-[[Category: Wu, W G]]
+[[Category: Wu WG]]
-[[Category: Cobra]]
-[[Category: Crisp]]
-[[Category: Ion channel blocking]]
-[[Category: Natrin]]
-[[Category: Serine protease]]
-[[Category: Toxin]]

3mz8

From Proteopedia

Current revision

Crystal Structure of Zinc-Bound Natrin From Naja atra

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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