4b0p

From Proteopedia

(Difference between revisions)

Revision as of 05:53, 25 August 2022

Crystal structure of soman-aged human butyrylcholinesterase in complex with methyl 2-(pentafluorobenzyloxyimino)pyridinium

Structural highlights

4b0p is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , ,
NonStd Res:
Related:	1eho, 1ehq, 1kcj, 1p0i, 1p0m, 1p0p, 1p0q, 1xlu, 1xlv, 1xlw, 2j4c, 2wid, 2wif, 2wig, 2wij, 2wik, 2wil, 2wsl, 2xmb, 2xmc, 2xmd, 2xmg, 2xqf, 2xqg, 2xqi, 2xqj, 2xqk, 2y1k, 4aqd, 4axb, 4b0o
Activity:	Cholinesterase, with EC number 3.1.1.8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CHLE_HUMAN] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:177400]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.

Function

[CHLE_HUMAN] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.^[1] ^[2]

Publication Abstract from PubMed

Organophosphorus nerve agents irreversibly inhibit cholinesterases. Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes. But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i.e., a conjugated enzyme that is no longer reactivable by oximes. One strategy to regain reactivability is to alkylate the phosphylic adduct. Specific alkylating molecules were synthesized and the crystal structures of the complexes they form with soman-aged human butyrylcholinesterase were solved. Although the compounds bind in the active site gorge of the aged enzyme, the orientation of the alkylating function appears to be unsuitable for efficient alkylation of the phosphylic adduct. However, these crystal structures provide key information to design efficient alkylators of aged-butyrylcholinesterase and specific reactivators of butyrylcholinesterase.

A step toward the reactivation of aged cholinesterases - Crystal structure of ligands binding to aged human butyrylcholinesterase.,Wandhammer M, de Koning M, van Grol M, Loiodice M, Saurel L, Noort D, Goeldner M, Nachon F Chem Biol Interact. 2012 Aug 16. PMID:22922115^[3]

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

References

↑ Chilukuri N, Duysen EG, Parikh K, diTargiani R, Doctor BP, Lockridge O, Saxena A. Adenovirus-transduced human butyrylcholinesterase in mouse blood functions as a bioscavenger of chemical warfare nerve agents. Mol Pharmacol. 2009 Sep;76(3):612-7. doi: 10.1124/mol.109.055665. Epub 2009 Jun, 19. PMID:19542320 doi:10.1124/mol.109.055665
↑ Amitay M, Shurki A. The structure of G117H mutant of butyrylcholinesterase: nerve agents scavenger. Proteins. 2009 Nov 1;77(2):370-7. doi: 10.1002/prot.22442. PMID:19452557 doi:10.1002/prot.22442
↑ Wandhammer M, de Koning M, van Grol M, Loiodice M, Saurel L, Noort D, Goeldner M, Nachon F. A step toward the reactivation of aged cholinesterases - Crystal structure of ligands binding to aged human butyrylcholinesterase. Chem Biol Interact. 2012 Aug 16. PMID:22922115 doi:10.1016/j.cbi.2012.08.005

1 Structural highlights
2 Disease
3 Function
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/4b0p"

@@ Line 3: / Line 3: @@
 <StructureSection load='4b0p' size='340' side='right'caption='[[4b0p]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4b0p]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B0P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4b0p]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B0P FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MF5:1-(1-METHYLPYRIDIN-1-IUM-2-YL)-N-[[2,3,4,5,6-PENTAKIS(FLUORANYL)PHENYL]METHOXY]METHANIMINE'>MF5</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MF5:1-(1-METHYLPYRIDIN-1-IUM-2-YL)-N-[[2,3,4,5,6-PENTAKIS(FLUORANYL)PHENYL]METHOXY]METHANIMINE'>MF5</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SBG:O-[(S)-HYDROXY(METHYL)PHOSPHORYL]-L-SERINE'>SBG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1eho|1eho]], [[1ehq|1ehq]], [[1kcj|1kcj]], [[1p0i|1p0i]], [[1p0m|1p0m]], [[1p0p|1p0p]], [[1p0q|1p0q]], [[1xlu|1xlu]], [[1xlv|1xlv]], [[1xlw|1xlw]], [[2j4c|2j4c]], [[2wid|2wid]], [[2wif|2wif]], [[2wig|2wig]], [[2wij|2wij]], [[2wik|2wik]], [[2wil|2wil]], [[2wsl|2wsl]], [[2xmb|2xmb]], [[2xmc|2xmc]], [[2xmd|2xmd]], [[2xmg|2xmg]], [[2xqf|2xqf]], [[2xqg|2xqg]], [[2xqi|2xqi]], [[2xqj|2xqj]], [[2xqk|2xqk]], [[2y1k|2y1k]], [[4aqd|4aqd]], [[4axb|4axb]], [[4b0o|4b0o]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1eho|1eho]], [[1ehq|1ehq]], [[1kcj|1kcj]], [[1p0i|1p0i]], [[1p0m|1p0m]], [[1p0p|1p0p]], [[1p0q|1p0q]], [[1xlu|1xlu]], [[1xlv|1xlv]], [[1xlw|1xlw]], [[2j4c|2j4c]], [[2wid|2wid]], [[2wif|2wif]], [[2wig|2wig]], [[2wij|2wij]], [[2wik|2wik]], [[2wil|2wil]], [[2wsl|2wsl]], [[2xmb|2xmb]], [[2xmc|2xmc]], [[2xmd|2xmd]], [[2xmg|2xmg]], [[2xqf|2xqf]], [[2xqg|2xqg]], [[2xqi|2xqi]], [[2xqj|2xqj]], [[2xqk|2xqk]], [[2y1k|2y1k]], [[4aqd|4aqd]], [[4axb|4axb]], [[4b0o|4b0o]]</div></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholinesterase Cholinesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.8 3.1.1.8] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Cholinesterase Cholinesterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.8 3.1.1.8] </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=4b0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b0p OCA], [http://pdbe.org/4b0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4b0p RCSB], [http://www.ebi.ac.uk/pdbsum/4b0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4b0p ProSAT]</span></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=4b0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b0p OCA], [https://pdbe.org/4b0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b0p RCSB], [https://www.ebi.ac.uk/pdbsum/4b0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b0p ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[http://omim.org/entry/177400 177400]]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
+[[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:[https://omim.org/entry/177400 177400]]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
 == Function ==
-[[http://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref>
+[[https://www.uniprot.org/uniprot/CHLE_HUMAN CHLE_HUMAN]] Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.<ref>PMID:19542320</ref> <ref>PMID:19452557</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 ==See Also==
-*[[Butyrylcholinesterase|Butyrylcholinesterase]]
+*[[Butyrylcholinesterase 3D structures|Butyrylcholinesterase 3D structures]]
 == References ==
 <references/>
@@ Line 31: / Line 31: @@
 </StructureSection>
 [[Category: Cholinesterase]]
-[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Goeldner, M]]
 [[Category: Grol, M van]]

4b0p

From Proteopedia

Revision as of 05:53, 25 August 2022

Crystal structure of soman-aged human butyrylcholinesterase in complex with methyl 2-(pentafluorobenzyloxyimino)pyridinium

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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