1k4y

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

spinqualitylabelsall models 1k4y, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: 4PN, MAN, NAG 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. 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxylesterase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA