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5lkr

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Revision as of 01:19, 16 November 2017

Human Butyrylcholinesterase complexed with N-Propargyliperidines

Structural highlights

5lkr is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
Gene:	BCHE, CHE1 (HUMAN)
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

In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines. All of these compounds inhibited hBChE with good selectivity over the related enzyme, acetylcholinesterase, and crossed the blood-brain barrier in a parallel artificial membrane permeation assay. The crystal structure of one of the inhibitors (compound 3) in complex with hBChE revealed its binding mode. Three compounds (4, 5, 6) showed concomitant inhibition of MAO-B. Additionally, the most potent hBChE inhibitor 7 and dual BChE and MAO-B inhibitor 6 were non-cytotoxic and protected neuronal SH-SY5Y cells from toxic amyloid beta-peptide species.

N-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer's agents.,Kosak U, Knez D, Coquelle N, Brus B, Pislar A, Nachon F, Brazzolotto X, Kos J, Colletier JP, Gobec S Bioorg Med Chem. 2016 Nov 19. pii: S0968-0896(16)30909-9. doi:, 10.1016/j.bmc.2016.11.032. PMID:27908752^[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
↑ Kosak U, Knez D, Coquelle N, Brus B, Pislar A, Nachon F, Brazzolotto X, Kos J, Colletier JP, Gobec S. N-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer's agents. Bioorg Med Chem. 2016 Nov 19. pii: S0968-0896(16)30909-9. doi:, 10.1016/j.bmc.2016.11.032. PMID:27908752 doi:http://dx.doi.org/10.1016/j.bmc.2016.11.032

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/5lkr"

@@ Line 3: / Line 3: @@
 <StructureSection load='5lkr' size='340' side='right' caption='[[5lkr]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5lkr]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LKR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LKR FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5lkr]] is a 2 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=5LKR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LKR FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6YC:~{N}-(2-METHOXYETHYL)-~{N}-[[(3~{S})-1-PROP-2-YNYLPIPERIDIN-3-YL]METHYL]NAPHTHALENE-2-CARBOXAMIDE'>6YC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BCHE, CHE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=5lkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lkr OCA], [http://pdbe.org/5lkr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lkr RCSB], [http://www.ebi.ac.uk/pdbsum/5lkr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lkr ProSAT]</span></td></tr>
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[Category: Cholinesterase]]
+[[Category: Human]]
 [[Category: Colletier, J P]]
 [[Category: Coquelle, N]]

5lkr

From Proteopedia

Revision as of 01:19, 16 November 2017

Human Butyrylcholinesterase complexed with N-Propargyliperidines

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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