1k4y
From Proteopedia
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| - | [[Image:1k4y.gif|left|200px]] | + | [[Image:1k4y.gif|left|200px]] |
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| - | '''Crystal Structure of Rabbit Liver Carboxylesterase in Complex with 4-piperidino-piperidine''' | + | {{Structure |
| + | |PDB= 1k4y |SIZE=350|CAPTION= <scene name='initialview01'>1k4y</scene>, resolution 2.50Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=4PN:4-PIPERIDINO-PIPERIDINE'>4PN</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of Rabbit Liver Carboxylesterase in Complex with 4-piperidino-piperidine''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1K4Y is a [ | + | 1K4Y is a [[Single protein]] structure of sequence from [http://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]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11967565 11967565] |
[[Category: Carboxylesterase]] | [[Category: Carboxylesterase]] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
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[[Category: side door]] | [[Category: side door]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:12:40 2008'' |
Revision as of 10:12, 20 March 2008
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| , resolution 2.50Å | |||||||
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| Ligands: | |||||||
| Activity: | Carboxylesterase, with EC number 3.1.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Rabbit Liver Carboxylesterase in Complex with 4-piperidino-piperidine
Overview
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.
About this Structure
1K4Y is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
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
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