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1e66

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Revision as of 10:30, 11 September 2015

STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH (-)-HUPRINE X AT 2.1A RESOLUTION

Structural highlights

1e66 is a 1 chain structure with sequence from Torpedo californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3ace, 2dfp, 2ace, 2ack, 1vxo, 1vxr, 1vot, 1som, 1qti, 1qig, 1qih, 1qii, 1qij, 1qik, 1qim, 1qid, 1qie, 1qif, 1oce, 1fss, 1eve, 1eea, 1dx6, 1cfj, 1ax9, 1amn, 1e3q, 4ace, 1acj, 1acl
Activity:	Acetylcholinesterase, with EC number 3.1.1.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[ACES_TORCA] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.

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

Huprine X is a novel acetylcholinesterase (AChE) inhibitor, with one of the highest affinities reported for a reversible inhibitor. It is a synthetic hybrid that contains the 4-aminoquinoline substructure of one anti-Alzheimer drug, tacrine, and a carbobicyclic moiety resembling that of another AChE inhibitor, (-)-huperzine A. Cocrystallization of huprine X with Torpedo californica AChE yielded crystals whose 3D structure was determined to 2.1 A resolution. The inhibitor binds to the anionic site and also hinders access to the esteratic site. Its aromatic portion occupies the same binding site as tacrine, stacking between the aromatic rings of Trp84 and Phe330, whereas the carbobicyclic unit occupies the same binding pocket as (-)-huperzine A. Its chlorine substituent was found to lie in a hydrophobic pocket interacting with rings of the aromatic residues Trp432 and Phe330 and with the methyl groups of Met436 and Ile439. Steady-state inhibition data show that huprine X binds to human AChE and Torpedo AChE 28- and 54-fold, respectively, more tightly than tacrine. This difference stems from the fact that the aminoquinoline moiety of huprine X makes interactions similar to those made by tacrine, but additional bonds to the enzyme are made by the huperzine-like substructure and the chlorine atom. Furthermore, both tacrine and huprine X bind more tightly to Torpedo than to human AChE, suggesting that their quinoline substructures interact better with Phe330 than with Tyr337, the corresponding residue in the human AChE structure. Both (-)-huperzine A and huprine X display slow binding properties, but only binding of the former causes a peptide flip of Gly117.

3D structure of Torpedo californica acetylcholinesterase complexed with huprine X at 2.1 A resolution: kinetic and molecular dynamic correlates.,Dvir H, Wong DM, Harel M, Barril X, Orozco M, Luque FJ, Munoz-Torrero D, Camps P, Rosenberry TL, Silman I, Sussman JL Biochemistry. 2002 Mar 5;41(9):2970-81. PMID:11863435^[1]

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

References

↑ Dvir H, Wong DM, Harel M, Barril X, Orozco M, Luque FJ, Munoz-Torrero D, Camps P, Rosenberry TL, Silman I, Sussman JL. 3D structure of Torpedo californica acetylcholinesterase complexed with huprine X at 2.1 A resolution: kinetic and molecular dynamic correlates. Biochemistry. 2002 Mar 5;41(9):2970-81. PMID:11863435

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/1e66"

@@ Line 6: / Line 6: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ace|3ace]], [[2dfp|2dfp]], [[2ace|2ace]], [[2ack|2ack]], [[1vxo|1vxo]], [[1vxr|1vxr]], [[1vot|1vot]], [[1som|1som]], [[1qti|1qti]], [[1qig|1qig]], [[1qih|1qih]], [[1qii|1qii]], [[1qij|1qij]], [[1qik|1qik]], [[1qim|1qim]], [[1qid|1qid]], [[1qie|1qie]], [[1qif|1qif]], [[1oce|1oce]], [[1fss|1fss]], [[1eve|1eve]], [[1eea|1eea]], [[1dx6|1dx6]], [[1cfj|1cfj]], [[1ax9|1ax9]], [[1amn|1amn]], [[1e3q|1e3q]], [[4ace|4ace]], [[1acj|1acj]], [[1acl|1acl]]</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=1e66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e66 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1e66 RCSB], [http://www.ebi.ac.uk/pdbsum/1e66 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=1e66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e66 OCA], [http://pdbe.org/1e66 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1e66 RCSB], [http://www.ebi.ac.uk/pdbsum/1e66 PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1e66" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[AChE inhibitors and substrates|AChE inhibitors and substrates]]
-*[[AChE inhibitors and substrates (Part II)|AChE inhibitors and substrates (Part II)]]
 *[[Acetylcholinesterase|Acetylcholinesterase]]
 == References ==

1e66

From Proteopedia

Revision as of 10:30, 11 September 2015

STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH (-)-HUPRINE X AT 2.1A RESOLUTION

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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