2x8b

From Proteopedia

(Difference between revisions)

Revision as of 17:58, 4 August 2016

CRYSTAL STRUCTURE OF HUMAN ACETYLCHOLINESTERASE INHIBITED BY AGED TABUN AND COMPLEXED WITH FASCICULIN-II

Structural highlights

2x8b is a 2 chain structure with sequence from Dendroaspis angusticeps and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
NonStd Res:
Related:	1fsc, 1mah, 1ku6, 2clj, 1b41, 1puv, 1fss, 1puw, 1vzj, 1f8u
Activity:	Acetylcholinesterase, with EC number 3.1.1.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.^[1] ^[2] ^[3] ^[4] [TXFA2_DENAN] This three-finger toxin selectively binds and inhibits with a 1:1 stoichiometry the mammalian and electric fish acetylcholinesterase (AChE) at picomolar concentrations. It is highly specific for the peripheral site on acetylcholinesterase. It has been called fasciculin since after injection into mice it cause severe, generalized and long-lasting (5-7 hours) fasciculations. The whole venom has anticoagulant activity, and the various components seem to act synergistically.

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

Tabun is a warfare agent that inhibits human acetylcholinesterase (hAChE) by rapid phosphylation of the catalytic serine. A time-dependent reaction occurs on the tabun adduct, leading to an "aged" enzyme, resistant to oxime reactivators. The aging reaction may proceed via either dealkylation or deamidation, depending on the stereochemistry of the phosphoramidyl adduct. We solved the X-ray structure of aged tabun-hAChE complexed with fasciculin II, and we show that aging proceeds through O-dealkylation, in agreement with the aging mechanism that we determined for tabun-inhibited human butyrylcholinesterase and mouse acetylcholinesterase. Noteworthy, aging and binding of fasciculin II lead to an improved thermostability, resulting from additional stabilizing interactions between the two subdomains that face each other across the active site gorge. This first structure of hAChE inhibited by a nerve agent provides structural insight into the inhibition and aging mechanisms and a structural template for the design of molecules capable of reactivating aged hAChE.

Structural Evidence That Human Acetylcholinesterase Inhibited by Tabun Ages through O-Dealkylation.,Carletti E, Colletier JP, Dupeux F, Trovaslet M, Masson P, Nachon F J Med Chem. 2010 Apr 21. PMID:20408548^[5]

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

References

↑ Chhajlani V, Derr D, Earles B, Schmell E, August T. Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase. FEBS Lett. 1989 Apr 24;247(2):279-82. PMID:2714437
↑ Velan B, Grosfeld H, Kronman C, Leitner M, Gozes Y, Lazar A, Flashner Y, Marcus D, Cohen S, Shafferman A. The effect of elimination of intersubunit disulfide bonds on the activity, assembly, and secretion of recombinant human acetylcholinesterase. Expression of acetylcholinesterase Cys-580----Ala mutant. J Biol Chem. 1991 Dec 15;266(35):23977-84. PMID:1748670
↑ Shafferman A, Kronman C, Flashner Y, Leitner M, Grosfeld H, Ordentlich A, Gozes Y, Cohen S, Ariel N, Barak D, et al.. Mutagenesis of human acetylcholinesterase. Identification of residues involved in catalytic activity and in polypeptide folding. J Biol Chem. 1992 Sep 5;267(25):17640-8. PMID:1517212
↑ Yang L, He HY, Zhang XJ. Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neurosci Res. 2002 Apr;42(4):261-8. PMID:11985878
↑ Carletti E, Colletier JP, Dupeux F, Trovaslet M, Masson P, Nachon F. Structural Evidence That Human Acetylcholinesterase Inhibited by Tabun Ages through O-Dealkylation. J Med Chem. 2010 Apr 21. PMID:20408548 doi:10.1021/jm901853b

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/2x8b"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF HUMAN ACETYLCHOLINESTERASE INHIBITED BY AGED TABUN AND COMPLEXED WITH FASCICULIN-II==
 <StructureSection load='2x8b' size='340' side='right' caption='[[2x8b]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2x8b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Dendroaspis_angusticeps Dendroaspis angusticeps] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8B FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2x8b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Dendroaspis_angusticeps Dendroaspis angusticeps] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X8B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X8B FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEN:O-[N,N-DIMETHYLPHOSPHORAMIDATE]-L-SERINE'>SEN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fsc|1fsc]], [[1mah|1mah]], [[1ku6|1ku6]], [[2clj|2clj]], [[1b41|1b41]], [[1puv|1puv]], [[1fss|1fss]], [[1puw|1puw]], [[1vzj|1vzj]], [[1f8u|1f8u]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </span></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=2x8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x8b RCSB], [http://www.ebi.ac.uk/pdbsum/2x8b PDBsum]</span></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=2x8b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8b OCA], [http://pdbe.org/2x8b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x8b RCSB], [http://www.ebi.ac.uk/pdbsum/2x8b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8b ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2x8b ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 30: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2x8b" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Acetylcholinesterase|Acetylcholinesterase]]
 *[[Fasciculin|Fasciculin]]
+*[[3D structures of acetylcholinesterase|3D structures of acetylcholinesterase]]
 == References ==
 <references/>
@@ Line 39: / Line 42: @@
 [[Category: Acetylcholinesterase]]
 [[Category: Dendroaspis angusticeps]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Carletti, E]]
 [[Category: Colletier, J P]]

2x8b

From Proteopedia

Revision as of 17:58, 4 August 2016

CRYSTAL STRUCTURE OF HUMAN ACETYLCHOLINESTERASE INHIBITED BY AGED TABUN AND COMPLEXED WITH FASCICULIN-II

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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