Two-state transition between molten globule and unfolded states of acetylcholinesterase as monitored by electron paramagnetic resonance spectroscopy.


Abstract

Cys-231 of Torpedo californica acetylcholinesterase (EC 3.1.1.7) was selectively labeled with the mercury derivative of a stable nitroxyl radical. In 1.5 M guanidinium chloride, this conjugate exists in a molten globule state (MG), whereas in 5 M denaturant, it is in an unfolded state (U). The transition between the two states is reversible. In the MG, the label is highly immobilized, whereas in the U, it is almost freely rotating. The clearly distinct electron paramagnetic resonance (EPR) spectra of the two states permits the study of this transition. Upon elevating the guanidinium chloride concentration, a decrease in the EPR signal of the MG occurs concomitantly with an increase in the U signal, the total intensity of the EPR spectra remaining constant. This behavior is characteristic of a two-state transition. The thermodynamic characteristics of this transition (delta G0 and m), whether estimated directly from the EPR data or from both CD and fluorescence data analyzed by assuming a two-state scheme, are in good agreement. Study holds ProTherm entries: 10584, 10585, 10586 Extra Details: molten globule state; electron paramagnetic resonance; two-state transition

Submission Details

ID: qkjAzXmS

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:40 p.m.

Version: 1

Publication Details
Kreimer DI;Szosenfogel R;Goldfarb D;Silman I;Weiner L,Proc. Natl. Acad. Sci. U.S.A. (1994) Two-state transition between molten globule and unfolded states of acetylcholinesterase as monitored by electron paramagnetic resonance spectroscopy. PMID:7991597
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
6G1U 2018-04-04 1.79 Crystal structure of Torpedo Californica acetylcholinesterase in complex with 9-Amino-6-chloro-1,2,3,4-tetrahydro-10-methylacridin-10-ium
1EA5 2000-11-08 1.8 NATIVE ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA at 1.8A resolution
6G1V 2018-04-04 1.82 Crystal structure of Torpedo Californica acetylcholinesterase in complex with 12-Amino-3-chloro-6,7,10,11-tetrahydro-5,9-dimethyl-7,11-methanocycloocta[b]quinolin-5-ium
6H14 2019-05-15 1.86 Crystal structure of TcACHE complexed to 1-(6-oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(4-(1-(2-((1,2,3,4-tetrahydroacridin-9-yl)amino)ethyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)urea
6G1W 2018-04-04 1.9 Crystal structure of Torpedo Californica acetylcholinesterase in complex with 2-{1-[2-(6-Chloro-1,2,3,4-tetrahydroacridin-9-ylamino)ethyl]-1H-1,2,3-triazol-4-yl}-N-[4-(hydroxy)-3-methoxybenzyl]acetamide
2C5G 2006-06-14 1.95 Torpedo californica acetylcholinesterase in complex with 20mM thiocholine
2WFZ 2009-08-11 1.95 NON-AGED CONJUGATE OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE WITH SOMAN
2WG2 2010-04-21 1.95 NON-AGED CONJUGATE OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE WITH SOMAN (ALTERNATIVE REFINEMENT)
6EUE 2018-11-14 2.0 Rivastigmine analogue bound to Tc ACHE.
1QID 2000-01-28 2.05 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT A) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
1W6R 2004-11-25 2.05 Complex of TcAChE with galanthamine derivative
1ZGC 2005-08-16 2.1 Crystal Structure of Torpedo Californica Acetylcholinesterase in Complex With an (RS)-Tacrine(10)-Hupyridone Inhibitor.
1E66 2001-08-02 2.1 STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH (-)-HUPRINE X AT 2.1A RESOLUTION
5EHX 2016-11-09 2.1 Crystal structure of MSF-aged Torpedo californica Acetylcholinesterase
5EI5 2016-11-09 2.1 Crystal structure of MSF-aged Torpedo californica Acetylcholinesterase in complex with alkylene-linked bis-tacrine dimer (7 carbon linker)
1GPK 2002-08-29 2.1 Structure of Acetylcholinesterase Complex with (+)-Huperzine A at 2.1A Resolution
1QIE 2000-01-28 2.1 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT B) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
1QIF 2000-01-28 2.1 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT C) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
2CKM 2006-09-04 2.15 Torpedo californica acetylcholinesterase complexed with alkylene- linked bis-tacrine dimer (7 carbon linker)
2C4H 2006-06-14 2.15 Torpedo californica acetylcholinesterase in complex with 500mM acetylthiocholine
1H23 2002-12-23 2.15 Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with (S,S)-(-)-bis(12)-hupyridone at 2.15A resolution
1H22 2002-12-23 2.15 Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with (S,S)-(-)-bis(10)-hupyridone at 2.15A resolution
1W4L 2004-11-25 2.16 Complex of TcAChE with bis-acting galanthamine derivative
5NAP 2018-05-02 2.17 Torpedo californica acetylcholinesterase in complex with a non-chiral donepezil-like inhibitor 17
3I6Z 2010-01-12 2.19 3D Structure of Torpedo californica acetylcholinesterase complexed with N-saccharinohexyl-galanthamine
1ODC 2005-03-23 2.2 STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH N-4'-QUINOLYL-N'-9'-(1',2',3',4'-TETRAHYDROACRIDINYL)-1,8- DIAMINOOCTANE AT 2.2A RESOLUTION
1SOM 1999-06-25 2.2 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE INHIBITED BY NERVE AGENT GD (SOMAN).
2WG1 2009-08-11 2.2 TERNARY COMPLEX OF THE AGED CONJUGATE OF TORPEDO CALIFORNICA ACEYLCHOLINESTERASE WITH SOMAN AND 2-PAM
2CEK 2006-04-10 2.2 Conformational Flexibility in the Peripheral Site of Torpedo californica Acetylcholinesterase Revealed by the Complex Structure with a Bifunctional Inhibitor
6H12 2019-05-15 2.2 Crystal structure of TcACHE complexed to 1-(6-Oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)-3-(4-(((1-(2-((1,2,3,4-tetrahydroacridin-9-yl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)methyl)pyridin-2-yl)urea
2WG0 2009-08-11 2.2 AGED CONJUGATE OF TORPEDO CALIFORNICA ACETYLCHOLINESTERASE WITH SOMAN (OBTAINED BY IN CRYSTALLO AGING)
6G17 2018-08-29 2.2 Non-aged form of Torpedo californica acetylcholinesterase inhibited by nerve agent tabun
6EZG 2018-11-21 2.2 Torpedo californica AChE in complex with indolic multi-target directed ligand
1GQR 2002-03-15 2.2 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH RIVASTIGMINE
2VT7 2008-07-22 2.2 Native Torpedo californica acetylcholinesterase collected with a cumulated dose of 800000 Gy
1VXR 1999-11-15 2.2 O-ETHYLMETHYLPHOSPHONYLATED ACETYLCHOLINESTERASE OBTAINED BY REACTION WITH O-ETHYL-S-[2-[BIS(1-METHYLETHYL)AMINO]ETHYL] METHYLPHOSPHONOTHIOATE (VX)
6EUC 2018-11-14 2.22 Reactivating oxime bound to Tc AChE's catalytic gorge.
6EWK 2018-11-14 2.22 T. californica AChE in complex with a 3-hydroxy-2-pyridine aldoxime.
5NAU 2018-05-02 2.25 Torpedo californica acetylcholinesterase in complex with a non-chiral donepezil-like compound 20
3ZV7 2012-05-23 2.26 Torpedo californica Acetylcholinesterase Inhibition by Bisnorcymserine
3I6M 2010-01-12 2.26 3D Structure of Torpedo californica acetylcholinesterase complexed with N-piperidinopropyl-galanthamine
1W76 2004-11-25 2.3 Orthorhombic form of Torpedo californica acetylcholinesterase (AChE) complexed with bis-acting galanthamine derivative
2C58 2006-06-14 2.3 Torpedo californica acetylcholinesterase in complex with 20mM acetylthiocholine
6FQN 2018-08-29 2.3 Carbamylated T. californica acetylcholineterase bound to uncharged hybrid reactivator 2
1JJB 2002-07-17 2.3 A neutral molecule in cation-binding site: Specific binding of PEG-SH to Acetylcholinesterase from Torpedo californica
1QIG 2000-01-28 2.3 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT D) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
2XI4 2011-03-23 2.3 Torpedo californica Acetylcholinesterase in Complex with Aflatoxin B1 (Orthorhombic Space Group)
2VJC 2008-07-22 2.3 Torpedo Californica Acetylcholinesterase In Complex With A Non Hydrolysable Substrate Analogue, 4-Oxo-N,N,N- Trimethylpentanaminium - Orthorhombic space group - Dataset A at 150K
1ZGB 2005-08-16 2.3 Crystal Structure of Torpedo Californica Acetylcholinesterase in Complex With an (R)-Tacrine(10)-Hupyridone Inhibitor.
1DX6 2000-01-02 2.3 STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH (-)-GALANTHAMINE AT 2.3A RESOLUTION
2VJA 2008-07-22 2.3 Torpedo Californica Acetylcholinesterase In Complex With A Non Hydrolysable Substrate Analogue, 4-Oxo-N,N,N- Trimethylpentanaminium - Orthorhombic space group - Dataset A at 100K
2VJD 2008-07-22 2.3 Torpedo Californica Acetylcholinesterase In Complex With A Non Hydrolysable Substrate Analogue, 4-Oxo-N,N,N- Trimethylpentanaminium - Orthorhombic space group - Dataset C at 150K
4TVK 2014-10-08 2.3 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A CHLOROTACRINE-JUGLONE HYBRID INHIBITOR
2DFP 1999-06-28 2.3 X-RAY STRUCTURE OF AGED DI-ISOPROPYL-PHOSPHORO-FLUORIDATE (DFP) BOUND TO ACETYLCHOLINESTERASE
3M3D 2011-03-09 2.34 Crystal structure of Acetylcholinesterase in complex with Xenon
1GPN 2002-08-29 2.35 STRUCTURE OF ACETYLCHOLINESTERASE COMPLEXED WITH HUPERZINE B AT 2.35A RESOLUTION
2VJB 2008-07-22 2.39 Torpedo Californica Acetylcholinesterase In Complex With A Non Hydrolysable Substrate Analogue, 4-Oxo-N,N,N- Trimethylpentanaminium - Orthorhombic space group - Dataset D at 100K
3GEL 2010-09-22 2.39 O-Methylphosphorylated Torpedo Acetylcholinesterase Obtained by Reaction with Methyl Paraoxon (AGED)
2V97 2007-11-20 2.4 Structure of the unphotolysed complex of TcAChE with 1-(2- nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine after a 9 seconds annealing to room temperature
2BAG 2006-08-29 2.4 3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine
1W75 2004-11-25 2.4 Native Orthorhombic form of Torpedo californica acetylcholinesterase (AChE)
5IH7 2017-04-05 2.4 Acetylcholinesterase of Torpedo californica in complex with the N-methyl-indoxylacetate hydrolysis products
2VA9 2007-11-20 2.4 Structure of native TcAChE after a 9 seconds annealing to room temperature during the first 5 seconds of which laser irradiation at 266nm took place
2VT6 2008-07-22 2.4 Native Torpedo californica acetylcholinesterase collected with a cumulated dose of 9400000 Gy
2V96 2007-11-20 2.4 Structure of the unphotolysed complex of TcAChE with 1-(2- nitrophenyl)-2,2,2-trifluoroethyl-arsenocholine at 100K
1VXO 1999-11-15 2.4 METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ETHYL-S-[2-[BIS(1-METHYLETHYL)AMINO]ETHYL] METHYLPHOSPHONOTHIOATE (VX)
2ACK 1998-02-11 2.4 ACETYLCHOLINESTERASE COMPLEXED WITH EDROPHONIUM, MONOCHROMATIC DATA
6FLD 2018-08-29 2.4 Carbamylated T. californica acetylcholineterase bound to uncharged hybrid reactivator 1
1UT6 2005-04-21 2.4 Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with N-9-(1',2',3',4'-Tetrahydroacridinyl)-1,8- diaminooctane at 2.4 angstroms resolution.
5E4T 2016-03-30 2.43 Acetylcholinesterase Methylene Blue with PEG
5BWC 2015-09-09 2.45 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA IN COMPLEX WITH THE BIS-PYRIDINIUM OXIME ORTHO-7
1HBJ 2001-09-25 2.5 X-ray Crystal structure of complex between Torpedo californica AChE and a reversible inhibitor, 4-Amino-5-fluoro-2-methyl-3-(3-trifluoroacetylbenzylthiomethyl)quinoline
5NUU 2018-05-30 2.5 Torpedo californica acetylcholinesterase in complex with a chlorotacrine-tryptophan hybrid inhibitor
1VOT 1997-06-16 2.5 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH HUPERZINE A
1QIH 2000-01-28 2.5 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT E) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
1EVE 1999-01-20 2.5 THREE DIMENSIONAL STRUCTURE OF THE ANTI-ALZHEIMER DRUG, E2020 (ARICEPT), COMPLEXED WITH ITS TARGET ACETYLCHOLINESTERASE
1QTI 1999-12-29 2.5 Acetylcholinesterase (E.C.3.1.1.7)
2CMF 2006-09-04 2.5 Torpedo californica acetylcholinesterase complexed with alkylene- linked bis-tacrine dimer (5 carbon linker)
2ACE 1996-11-08 2.5 NATIVE ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA
5E4J 2016-03-30 2.54 Acetylcholinesterase Methylene Blue no PEG
5BWB 2015-09-09 2.57 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA IN COMPLEX WITH THE BIS-IMIDAZOLIUM OXIME 2BIM-7
1CFJ 1999-06-25 2.6 METHYLPHOSPHONYLATED ACETYLCHOLINESTERASE (AGED) OBTAINED BY REACTION WITH O-ISOPROPYLMETHYLPHOSPHONOFLUORIDATE (GB, SARIN)
2J3D 2008-06-24 2.6 Native monoclinic form of Torpedo acetylcholinesterase
2C5F 2006-06-14 2.6 Torpedo californica acetylcholinesterase in complex with a non hydrolysable substrate analogue, 4-oxo-N,N,N-trimethylpentanaminium
4X3C 2015-12-23 2.6 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A TACRINE-NICOTINAMIDE HYBRID INHIBITOR
6EZH 2018-11-21 2.6 Torpedo californica AChE in complex with indolic multi-target directed ligand
1U65 2005-07-19 2.61 Ache W. CPT-11
6G4M 2018-08-29 2.63 Torpedo californica acetylcholinesterase bound to uncharged hybrid reactivator 1
1QII 2000-01-28 2.65 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT F) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
5E2I 2016-03-30 2.65 Acetylcholinesterase Methylene Blue no PEG
2W6C 2009-04-07 2.69 ACHE IN COMPLEX WITH A BIS-(-)-NOR-MEPTAZINOL DERIVATIVE
5DLP 2016-03-30 2.7 Acetylcholinesterase Methylene Blue no PEG
1OCE 1999-05-18 2.7 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH MF268
2VQ6 2008-05-13 2.71 Torpedo californica acetylcholinesterase complexed with 2-PAM
6G4O 2018-08-29 2.78 Non-aged form of Torpedo californica acetylcholinesterase inhibited by tabun analog NEDPA bound to uncharged reactivator 1
1ACJ 1994-08-31 2.8 QUATERNARY LIGAND BINDING TO AROMATIC RESIDUES IN THE ACTIVE-SITE GORGE OF ACETYLCHOLINESTERASE
1AMN 1996-04-03 2.8 TRANSITION STATE ANALOG: ACETYLCHOLINESTERASE COMPLEXED WITH M-(N,N,N-TRIMETHYLAMMONIO)TRIFLUOROACETOPHENONE
1ACL 1994-08-31 2.8 QUATERNARY LIGAND BINDING TO AROMATIC RESIDUES IN THE ACTIVE-SITE GORGE OF ACETYLCHOLINESTERASE
2J4F 2006-09-05 2.8 Torpedo acetylcholinesterase - Hg heavy-atom derivative
2J3Q 2007-09-04 2.8 Torpedo acetylcholinesterase complexed with fluorophore thioflavin T
4W63 2015-09-09 2.8 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE IN COMPLEX WITH A TACRINE-BENZOFURAN HYBRID INHIBITOR
1AX9 1998-02-11 2.8 ACETYLCHOLINESTERASE COMPLEXED WITH EDROPHONIUM, LAUE DATA
6H13 2019-05-15 2.8 Crystal structure of TcACHE complexed to1-(4-((Methyl((1-(2-((1,2,3,4-tetrahydroacridin-9-yl)amino)ethyl)-1H-1,2,3-triazol-4-yl)methyl)amino)methyl)pyridin-2-yl)-3-(6-oxo-1,2,3,4,6,10b-hexahydropyrido[2,1-a]isoindol-10-yl)urea
1QIJ 2000-01-28 2.8 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT G) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
6G4P 2018-08-29 2.83 Non-aged form of Torpedo californica acetylcholinesterase inhibited by tabun analog NEDPA bound to uncharged reactivator 2
1E3Q 2000-07-03 2.85 TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH BW284C51
1QIK 2000-01-28 2.9 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT H) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
6G4N 2018-08-29 2.9 Torpedo californica acetylcholinesterase bound to uncharged hybrid reactivator 2
2V98 2007-11-20 3.0 Structure of the complex of TcAChE with 1-(2-nitrophenyl)-2,2,2- trifluoroethyl-arsenocholine after a 9 seconds annealing to room temperature, during the first 5 seconds of which laser irradiation at 266nm took place
1FSS 1996-03-08 3.0 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH FASCICULIN-II
1QIM 2000-01-28 3.0 SPECIFIC CHEMICAL AND STRUCTURAL DAMAGE AT NINE TIME POINTS (POINT I) CAUSED BY INTENSE SYNCHROTRON RADIATION TO TORPEDO CALIFORNICA ACETYLCHOLINESTERASE
1GQS 2002-03-15 3.0 ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH NAP
1EEA 1999-02-01 4.5 Acetylcholinesterase

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
97.6 Acetylcholinesterase P07692 ACES_TORMA
100.0 Acetylcholinesterase P04058 ACES_TETCF