6nea: Difference between revisions

Latest revision as of 06:51, 11 October 2023

Human Acetylcholinesterase in complex with reactivator, HLo7

Structural highlights

6nea is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.419Å
Ligands:	FUC, HLO, NAG
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]

Publication Abstract from PubMed

The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLo-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLo-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLo-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.

Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate.,Hsu FL, Bae SY, McGuire J, Anderson DR, Bester SM, Height JJ, Pegan SD, Walz AJ ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi:, 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9. PMID:31097996^[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
↑ Hsu FL, Bae SY, McGuire J, Anderson DR, Bester SM, Height JJ, Pegan SD, Walz AJ. Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate. ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi:, 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9. PMID:31097996 doi:https://dx.doi.org/10.1021/acsmedchemlett.9b00021

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] Hsu FL, Bae SY, McGuire J, Anderson DR, Bester SM, Height JJ, Pegan SD, Walz AJ. Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate. ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi:, 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9. PMID:31097996 doi:https://dx.doi.org/10.1021/acsmedchemlett.9b00021

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6nea is ON HOLD
+==Human Acetylcholinesterase in complex with reactivator, HLo7==
+<StructureSection load='6nea' size='340' side='right'caption='[[6nea]], [[Resolution|resolution]] 2.42&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6nea]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NEA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NEA FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.419&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=HLO:1-[({2,4-BIS[(E)-(HYDROXYIMINO)METHYL]PYRIDINIUM-1-YL}METHOXY)METHYL]-4-CARBAMOYLPYRIDINIUM'>HLO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6nea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nea OCA], [https://pdbe.org/6nea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nea RCSB], [https://www.ebi.ac.uk/pdbsum/6nea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nea ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ACES_HUMAN ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.<ref>PMID:2714437</ref> <ref>PMID:1748670</ref> <ref>PMID:1517212</ref> <ref>PMID:11985878</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLo-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLo-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLo-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.
-Authors: Bester, S.M., McGuire, J., Height, J.J., Pegan, S.D.
+Synthesis and Molecular Properties of Nerve Agent Reactivator HLo-7 Dimethanesulfonate.,Hsu FL, Bae SY, McGuire J, Anderson DR, Bester SM, Height JJ, Pegan SD, Walz AJ ACS Med Chem Lett. 2019 Mar 28;10(5):761-766. doi:, 10.1021/acsmedchemlett.9b00021. eCollection 2019 May 9. PMID:31097996<ref>PMID:31097996</ref>
-Description: Human Acetylcholinesterase in complex with reactivator, HLo7
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Mcguire, J]]
+<div class="pdbe-citations 6nea" style="background-color:#fffaf0;"></div>
-[[Category: Pegan, S.D]]
-[[Category: Bester, S.M]]
+==See Also==
-[[Category: Height, J.J]]
+*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bester SM]]
+[[Category: Height JJ]]
+[[Category: McGuire J]]
+[[Category: Pegan SD]]

6nea: Difference between revisions

Latest revision as of 06:51, 11 October 2023

Human Acetylcholinesterase in complex with reactivator, HLo7

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools