1k4y: Difference between revisions

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<StructureSection load='1k4y' size='340' side='right'caption='[[1k4y]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='1k4y' size='340' side='right'caption='[[1k4y]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1k4y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/European_rabbit European rabbit]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K4Y FirstGlance]. <br>
<table><tr><td colspan='2'>[[1k4y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K4Y FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PN:4-PIPERIDINO-PIPERIDINE'>4PN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 2.5&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4PN:4-PIPERIDINO-PIPERIDINE'>4PN</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=1k4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k4y OCA], [https://pdbe.org/1k4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k4y RCSB], [https://www.ebi.ac.uk/pdbsum/1k4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k4y 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=1k4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k4y OCA], [https://pdbe.org/1k4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k4y RCSB], [https://www.ebi.ac.uk/pdbsum/1k4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k4y ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EST1_RABIT EST1_RABIT] Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.<ref>PMID:9635592</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k4y ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k4y ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian carboxylesterases cleave the anticancer prodrug CPT-11 (Irinotecan) into SN-38, a potent topoisomerase I poison, and 4-piperidino-piperidine (4PP). We present the 2.5 A crystal structure of rabbit liver carboxylesterase (rCE), the most efficient enzyme known to activate CPT-11 in this manner, in complex with the leaving group 4PP. 4PP is observed bound adjacent to a high-mannose Asn-linked glycosylation site on the surface of rCE. This product-binding site is separated from the catalytic gorge by a thin wall of amino acid side chains, suggesting that 4PP may be released through this secondary product exit pore. The crystallographic observation of a leaving group bound on the surface of rCE supports the 'back door' product exit site proposed for the acetylcholinesterases. These results may facilitate the design of improved anticancer drugs or enzymes for use in viral-directed cancer cotherapies.
Structural insights into CPT-11 activation by mammalian carboxylesterases.,Bencharit S, Morton CL, Howard-Williams EL, Danks MK, Potter PM, Redinbo MR Nat Struct Biol. 2002 May;9(5):337-42. PMID:11967565<ref>PMID:11967565</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1k4y" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Carboxylesterase]]
[[Category: European rabbit]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bencharit, S]]
[[Category: Oryctolagus cuniculus]]
[[Category: Danks, M K]]
[[Category: Bencharit S]]
[[Category: Howard-Williams, E L]]
[[Category: Danks MK]]
[[Category: Morton, C L]]
[[Category: Howard-Williams EL]]
[[Category: Potter, P M]]
[[Category: Morton CL]]
[[Category: Redinbo, M R]]
[[Category: Potter PM]]
[[Category: Camptothecin]]
[[Category: Redinbo MR]]
[[Category: Esterase]]
[[Category: Hydrolase]]
[[Category: Irinotecan]]
[[Category: Side door]]

Revision as of 10:57, 3 April 2024

Crystal Structure of Rabbit Liver Carboxylesterase in Complex with 4-piperidino-piperidineCrystal Structure of Rabbit Liver Carboxylesterase in Complex with 4-piperidino-piperidine

Structural highlights

1k4y is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EST1_RABIT Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.[1]

Evolutionary Conservation

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

See Also

References

  1. ↑ Potter PM, Pawlik CA, Morton CL, Naeve CW, Danks MK. Isolation and partial characterization of a cDNA encoding a rabbit liver carboxylesterase that activates the prodrug irinotecan (CPT-11). Cancer Res. 1998 Jun 15;58(12):2646-51 PMID:9635592

1k4y, resolution 2.50Å

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