1zgb

From Proteopedia

(Difference between revisions)

Revision as of 08:11, 15 May 2024

Crystal Structure of Torpedo Californica Acetylcholinesterase in Complex With an (R)-Tacrine(10)-Hupyridone Inhibitor.

Structural highlights

1zgb is a 1 chain structure with sequence from Tetronarce californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

ACES_TETCF Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Recently, alkylene-linked heterodimers of tacrine (1) and 5-amino-5,6,7,8-tetrahydroquinolinone (2, hupyridone) were shown to exhibit higher acetylcholinesterase (AChE) inhibition than either monomeric 1 or 2. Such inhibitors are potential drug candidates for ameliorating the cognitive decrements in early Alzheimer patients. In an attempt to understand the inhibition mechanism of one such dimer, (RS)-(+/-)-N-9-(1,2,3,4-tetrahydroacridinyl)-N'-5-[5,6,7,8-tetrahydro-2'(1 'H)-quinolinonyl]-1,10-diaminodecane [(RS)-(+/-)-3] bisoxalate, the racemate was soaked in trigonal Torpedo californica AChE (TcAChE) crystals, and the X-ray structure of the resulting complex was solved to 2.30 A resolution. Its structure revealed the 1 unit bound to the "anionic" subsite of the active site, near the bottom of the active-site gorge, as seen for the 1/TcAChE complex. Interestingly, only the (R)-enantiomer of the 2 unit was seen in the peripheral "anionic" site (PAS) at the top of the gorge, and was hydrogen-bonded to the side chains of residues belonging to an adjacent, symmetry-related AChE molecule covering the gorge entrance. When the same racemate was soaked in orthorhombic crystals of TcAChE, in which the entrance to the gorge is more exposed, the crystal structure of the corresponding complex revealed no substantial enantiomeric selectivity. This observation suggests that the apparent enantiomeric selectivity of trigonal crystals of TcAChE for (R)-3 is mainly due to crystal packing, resulting in preferential binding of one enantiomeric inhibitor both to its "host" enzyme and to its neighbor in the asymmetric unit, rather than to steric constraints imposed by the geometry of the active-site gorge.

Crystal packing mediates enantioselective ligand recognition at the peripheral site of acetylcholinesterase.,Haviv H, Wong DM, Greenblatt HM, Carlier PR, Pang YP, Silman I, Sussman JL J Am Chem Soc. 2005 Aug 10;127(31):11029-36. PMID:16076210^[1]

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

References

↑ Haviv H, Wong DM, Greenblatt HM, Carlier PR, Pang YP, Silman I, Sussman JL. Crystal packing mediates enantioselective ligand recognition at the peripheral site of acetylcholinesterase. J Am Chem Soc. 2005 Aug 10;127(31):11029-36. PMID:16076210 doi:http://dx.doi.org/10.1021/ja051765f

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/1zgb"

@@ Line 3: / Line 3: @@
 <StructureSection load='1zgb' size='340' side='right'caption='[[1zgb]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1zgb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZGB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1zgb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZGB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1E:(5R)-5-{[10-(1,2,3,4-TETRAHYDROACRIDIN-9-YLAMINO)DECYL]AMINO}-5,6,7,8-TETRAHYDROQUINOLIN-2(1H)-ONE'>A1E</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1zgc|1zgc]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1E:(5R)-5-{[10-(1,2,3,4-TETRAHYDROACRIDIN-9-YLAMINO)DECYL]AMINO}-5,6,7,8-TETRAHYDROQUINOLIN-2(1H)-ONE'>A1E</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acetylcholinesterase Acetylcholinesterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.7 3.1.1.7] </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=1zgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zgb OCA], [https://pdbe.org/1zgb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zgb RCSB], [https://www.ebi.ac.uk/pdbsum/1zgb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zgb ProSAT], [https://www.topsan.org/Proteins/ISPC/1zgb TOPSAN]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/ACES_TORCA ACES_TORCA]] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.
+[https://www.uniprot.org/uniprot/ACES_TETCF ACES_TETCF] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Acetylcholinesterase]]
 [[Category: Large Structures]]
-[[Category: Torpedo californica]]
+[[Category: Tetronarce californica]]
-[[Category: Carlier, P R]]
+[[Category: Carlier PR]]
-[[Category: Greenblatt, H M]]
+[[Category: Greenblatt HM]]
-[[Category: Haviv, H]]
+[[Category: Haviv H]]
-[[Category: ISPC, Israel Structural Proteomics Center]]
+[[Category: Pang YP]]
-[[Category: Pang, Y P]]
+[[Category: Silman I]]
-[[Category: Silman, I]]
+[[Category: Sussman JL]]
-[[Category: Sussman, J L]]
+[[Category: Wong DM]]
-[[Category: Wong, D M]]
-[[Category: Enantiomeric selectivity]]
-[[Category: Hydrolase]]
-[[Category: Protein-inhibitor complex]]
-[[Category: Serine-hydrolase]]
-[[Category: Structural genomic]]

1zgb

From Proteopedia

Revision as of 08:11, 15 May 2024

Crystal Structure of Torpedo Californica Acetylcholinesterase in Complex With an (R)-Tacrine(10)-Hupyridone Inhibitor.

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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