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| '''3D structure of acetylcholinesterase'''<br /> | | '''3D structure of acetylcholinesterase'''<br /> |
| The active site gorge has <scene name='Acetylcholinesterase/New_down_gorge/6'>two binding sites</scene>, a catalytic site (consisting of the catalytic triad together with Trp84 & Phe330) and a peripheral site (including Trp 279 & Tyr 121), which helps prebind the substrate and direct it toward the active site. The 3D structure showed not only that the active site was buried deep in the enzyme, but surprisingly, there were no negatively charged residues along this gorge, as was expected to help attract the positively charged ACh substrate, rather, instead, a series of aromatic residues that are highly conserved in all AChE sequences. See: [[AChE inhibitors and substrates]] | | The active site gorge has <scene name='Acetylcholinesterase/New_down_gorge/6'>two binding sites</scene>, a catalytic site (consisting of the catalytic triad together with Trp84 & Phe330) and a peripheral site (including Trp 279 & Tyr 121), which helps prebind the substrate and direct it toward the active site. The 3D structure showed not only that the active site was buried deep in the enzyme, but surprisingly, there were no negatively charged residues along this gorge, as was expected to help attract the positively charged ACh substrate, rather, instead, a series of aromatic residues that are highly conserved in all AChE sequences. See: [[AChE inhibitors and substrates]] |
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| ==Selected 3D Structures of AChE ==
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| ===Acetylcholinesterase - AChE native===
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| [[3lii]] – hAChE - recombinant human <br />
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| [[1ea5]], [[2ace]] – ''Tc''AChE – trigonal – ''Torpedo californica'' <br />
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| [[2j3d]] – ''Tc''AChE – monoclinic <br />
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| [[1w75]] – ''Tc''AChE – orthorhombic <br />
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| [[1eea]] – ''Tc''AChE – cubic <br />
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| [[2vt6]], [[2vt7]] – ''Tc''AChE – different dosage <br />
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| [[1qid]] to [[1qim]] - ''Tc''AChE synchrotron radiation damage <br />
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| [[1j06]], [[1maa]] – mAChE - mouse <br />
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| [[1qo9]] – ''Dm''AChE - ''Drosophila'' <br />
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| [[1c2o]], [[1c2b]] – electrophorus AChE – Electric eel <br />
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| ===AChE active site inhibitors conjugating at the bottom of the active site gorge===
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| [[2w9i]] – ''Tc''AChE + methylene blue <br />
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| [[2wls]] – MosAChE + AMTS13 <br />
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| [[2vq6]] – ''Tc''AChE + 2-PAM <br />
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| [[2j3q]] – ''Tc''AChE + Thioflavin T <br />
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| [[2ha0]] – mAChE + ketoamyltrimethylammonium <br />
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| [[2h9y]] – mAChE + TMTFA <br />
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| [[1gpk]], [[1gpn]], [[1vot]] – ''Tc''AChE + huperzine <br />
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| [[1gqr]] – ''Tc''AChE + rivastigmine <br />
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| [[1gqs]] – ''Tc''AChE + NAP <br />
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| [[1e66]] – ''Tc''AChE + huprine <br />
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| [[1dx4]], [[1qon]] – ''Dm''AChE + tacrine derivative <br />
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| [[1oce]] – ''Tc''AChE + MF268 <br />
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| [[1ax9]], [[1ack]] – ''Tc''AChE + edrophonium <br />
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| [[1amn]] – ''Tc''AChE + TMTFA <br />
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| [[1acj]] – ''Tc''AChE + tacrine <br />
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| ===AChE peripheral site inhibitors conjugating at the surface of the protein===
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| [[1ku6]] - mAChE + fasciculin 2 <br />
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| [[1ku6]], [[1mah]] - mAChE + fasciculin 2 <br />
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| [[1j07]] - mAChE + decidium <br />
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| [[1n5m]] - mAChE + gallamine <br />
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| [[1n5r]] - mAChE + propidium <br />
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| [[1b41]], [[1f8u]] - hAChE + fasciculin 2 <br />
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| [[1fss]] - TcAChE + fasciculin 2 <br />
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| ===AChE bis inhibitors spanning the active site gorge===
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| [[3i6m]] – ''Tc''AChE + N-piperidinopropyl galanthamine <br />
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| [[3i6z]] - ''Tc''AChE + saccharinohexyl galanthamine <br />
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| [[1zgb]], [[1zgc]] – ''Tc''AChE + tacrine (10) hupyridone <br />
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| [[2w6c]] – ''Tc''AChE + bis-(-)-nor-meptazinol <br />
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| [[2ckm]], [[2cmf]] – ''Tc''AChE + bis-tacrine <br />
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| [[2cek]] – ''Tc''AChE + N-[8-(1,2,3,4-tetrahydroacridin-9-ylthio)octyl]-1,2,3,4-tetrahydroacridin-9-amine <br />
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| [[1ut6]] - ''Tc''AChE + N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane <br />
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| [[1odc]] - ''Tc''AChE + N-4-quinolyl-N-9-(1,2,3,4-tetrahydroacridinyl)-1,8-diaminooctane <br />
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| [[1w4l]], [[1w6r]], [[1w76]], [[1dx6]], [[1qti]] - TcAChE + galanthamine and derivative <br />
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| [[1q83]], [[1q84]] - mAChE + TZ2PA6 <br />
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| [[1h22]], [[1h23]] – ''Tc''AChE + bis-hupyridone <br />
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| [[1hbj]] – ''Tc''AChE + quinoline derivativev <br />
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| [[1e3q]] – ''Tc''AChE + bw284c51 <br />
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| [[1eve]] – ''Tc''AChE + e2020 <br />
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| [[1acl]] – ''Tc''AChE + decamethonium <br />
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| ===AChE organophosphate inhibitors causing irreversible inhibition===
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| [[2wu3]] – mAChE + fenamiphos and HI-6 <br />
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| [[2wu4]] – mAChE + fenamiphos and ortho-7 <br />
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| [[2jgf]] - mAChE + fenamiphos <br />
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| [[2wfz]], [[2wg0]], [[1som]] - ''Tc''AChE + soman <br />
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| [[2wg1]] - ''Tc''AChE + soman + 2-PAM <br />
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| [[2whp]], [[2whq]], [[2whr]] – mAChE + sarin and HI-6 <br />
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| [[2jgg]] - mAChE + sarin <br />
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| [[2jgl]] - mAChE + VX and sarin <br />
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| [[1cfj]] - ''Tc''AChE + sarin, GB <br />
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| [[3dl4]], [[3dl7]] – mAChE + tabun <br />
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| [[2jey]] – mAChE + HLO-7 <br />
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| [[2c0p]], [[2c0q]] - mAChE + tabun <br />
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| [[2jez]] - mAChE + tabun + HLO-7 <br />
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| [[2jf0]] - mAChE + tabun + Ortho-7 <br />
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| [[2jgh]] - mAChE + VX <br />
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| [[1vxo]], [[1vxr]] - ''Tc''AChE + VX <br />
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| [[2jgi]], [[2jgm]] - mAChE + DFP <br />
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| [[1dfp]] - ''Tc''AChE + DFP <br />
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| [[2jgj]], [[2jgk]], [[2jge]] - mAChE + methamidophos <br />
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| [[2gyu]] - mAChE + HI-6 <br />
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| [[2gyv]] - mAChE + Ortho-7 <br />
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| [[2gyw]] - mAChE + obidoxime <br />
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| ===AChE substrate analogues mimicking the binding of the substrate acetylcholine===
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| [[2ha4]] – mAChE (mutant) + acetylcholine <br />
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| [[2vja]], [[2vjb]], [[2vjc]], [[2vjd]], [[2cf5]] – ''Tc''AChE + 4-oxo-N,N,N-trimethylpentanaminium <br />
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| [[2v96]], [[2v97]], [[2v98]], [[2v99]] – ''Tc''AChE + 1-(2-nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine <br />
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| [[2ha2]] – mAChE + succinylcholine <br />
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| [[2ha3]] - mAChE + choline <br />
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| [[2ha5]] – mAChE (mutant) + acetylthiocholine <br />
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| [[2ha6]] – mAChE (mutant) + succinylthiocholine <br />
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| [[2ha7]] – mAChE (mutant) + butyrylthiocholine <br />
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| [[2ch4]], [[2c58]] – ''Tc''AChE + acetylthiocholine <br />
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| [[2c5g]] – ''Tc''AChE + thiocholine <br />
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| ===Others...===
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| [[2j4f]] – ''Tc''AChE + Hg <br />
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| [[1vzj]] – ''Tc''AChE tetramerization domain <br />
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| [[1jjb]] – ''Tc''AChE + PEG <br />
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| More structures can be obtained by searching for
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| [http://proteopedia.org/wiki/index.php/Special:Search?search=AChE&fulltext=AChE AChE]
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| [[Category: catalytic triad]]
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| [[Category: cholinesterase]]
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| [[Category: cholinesterases]]
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| [[Category: acetylcholine]]
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| [[Category: cation-pi]]
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| [[Category: Alzheimers]]
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| [[Category: nerve gasses]]
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| ==External Links ==
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| [http://www.messiah.edu/departments/chemistry/molscilab/jtat_080120/acetylcholinesterase/contents/contents.htm Acetylcholinesterase Tutorial] by Karl Oberholser, Messiah College
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| [http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb54_1.html PDB Molecule of the Month - Acetylcholinesterase]
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| [http://www.weizmann.ac.il/sb/faculty_pages/Sussman/movies/Radiation_Damage Movies: X-ray Damage in ACh] & [http://www.weizmann.ac.il/sb/faculty_pages/Sussman/movies/richardnew.mpg Nature's Vacuum Cleaner] by R. Gillilan, Cornell Univ
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