2xqj

From Proteopedia

(Difference between revisions)

Revision as of 05:25, 10 August 2022

X-ray Structure of human butyrylcholinesterase inhibited by pure enantiomer VX-(R)

Structural highlights

2xqj is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , , , ,
Related:	2wsl, 2j4c, 2xmg, 2xmb, 1kcj, 2wik, 1p0p, 1xlu, 2wij, 2xmd, 1xlv, 1eho, 1p0m, 1xlw, 1ehq, 1p0q, 2xmc, 2wid, 2wil, 2wif, 1p0i, 2wig, 2xqk, 2xqi, 2xqg, 2xqf
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

Nerve agents are chiral organophosphate compounds (OPs) that exert their acute toxicity by phosphorylating the catalytic serine of acetylcholinesterase (AChE). The inhibited cholinesterases can be reactivated using oximes, but a spontaneous time-dependent process called aging alters the adduct, leading to resistance toward oxime reactivation. Human butyrylcholinesterase (BChE) functions as a bioscavenger, protecting the cholinergic system against OPs. The stereoselectivity of BChE is an important parameter for its efficiency at scavenging the most toxic OPs enantiomer for AChE. Crystals of BChE inhibited in solution or in cristallo with racemic V-agents (VX, Russian VX, and Chinese VX) systematically show the formation of the P(S) adduct. In this configuration, no catalysis of aging seems possible as confirmed by the three-dimensional structures of the three conjugates incubated over a period exceeding a week. Crystals of BChE soaked in optically pure VX(R)-(+) and VX(S)-(-) solutions lead to the formation of the P(S) and P(R) adduct, respectively. These structural data support an in-line phosphonylation mechanism. Additionally, they show that BChE reacts with VX(R)-(+) in the presence of racemic mixture of V-agents, at odds with earlier kinetic results showing a moderate higher inhibition rate for VX(S)-(-). These combined results suggest that the simultaneous presence of both enantiomers alters the enzyme stereoselectivity. In summary, the three-dimensional data show that BChE reacts preferentially with P(R) enantiomer of V-agents and does not age, in complete contrast to AChE, which is selectively inhibited by the P(S) enantiomer and ages.

Structural Study of the Complex Stereoselectivity of Human Butyrylcholinesterase for the Neurotoxic V-agents.,Wandhammer M, Carletti E, Van der Schans M, Gillon E, Nicolet Y, Masson P, Goeldner M, Noort D, Nachon F J Biol Chem. 2011 May 13;286(19):16783-9. Epub 2011 Mar 23. PMID:21454498^[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, Carletti E, Van der Schans M, Gillon E, Nicolet Y, Masson P, Goeldner M, Noort D, Nachon F. Structural Study of the Complex Stereoselectivity of Human Butyrylcholinesterase for the Neurotoxic V-agents. J Biol Chem. 2011 May 13;286(19):16783-9. Epub 2011 Mar 23. PMID:21454498 doi:10.1074/jbc.M110.209569

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2xqj"

@@ Line 3: / Line 3: @@
 <StructureSection load='2xqj' size='340' side='right'caption='[[2xqj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xqj]] 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=2XQJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2XQJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xqj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XQJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XQJ FirstGlance]. <br>
 </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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VX:O-ETHYLMETHYLPHOSPHONIC+ACID+ESTER+GROUP'>VX</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wsl|2wsl]], [[2j4c|2j4c]], [[2xmg|2xmg]], [[2xmb|2xmb]], [[1kcj|1kcj]], [[2wik|2wik]], [[1p0p|1p0p]], [[1xlu|1xlu]], [[2wij|2wij]], [[2xmd|2xmd]], [[1xlv|1xlv]], [[1eho|1eho]], [[1p0m|1p0m]], [[1xlw|1xlw]], [[1ehq|1ehq]], [[1p0q|1p0q]], [[2xmc|2xmc]], [[2wid|2wid]], [[2wil|2wil]], [[2wif|2wif]], [[1p0i|1p0i]], [[2wig|2wig]], [[2xqk|2xqk]], [[2xqi|2xqi]], [[2xqg|2xqg]], [[2xqf|2xqf]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2wsl|2wsl]], [[2j4c|2j4c]], [[2xmg|2xmg]], [[2xmb|2xmb]], [[1kcj|1kcj]], [[2wik|2wik]], [[1p0p|1p0p]], [[1xlu|1xlu]], [[2wij|2wij]], [[2xmd|2xmd]], [[1xlv|1xlv]], [[1eho|1eho]], [[1p0m|1p0m]], [[1xlw|1xlw]], [[1ehq|1ehq]], [[1p0q|1p0q]], [[2xmc|2xmc]], [[2wid|2wid]], [[2wil|2wil]], [[2wif|2wif]], [[1p0i|1p0i]], [[2wig|2wig]], [[2xqk|2xqk]], [[2xqi|2xqi]], [[2xqg|2xqg]], [[2xqf|2xqf]]</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://proteopedia.org/fgij/fg.htm?mol=2xqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xqj OCA], [http://pdbe.org/2xqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xqj RCSB], [http://www.ebi.ac.uk/pdbsum/2xqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xqj 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=2xqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xqj OCA], [https://pdbe.org/2xqj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xqj RCSB], [https://www.ebi.ac.uk/pdbsum/2xqj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xqj 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 ==

2xqj

From Proteopedia

Revision as of 05:25, 10 August 2022

X-ray Structure of human butyrylcholinesterase inhibited by pure enantiomer VX-(R)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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