2c1o
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(New page: 200px<br /> <applet load="2c1o" size="450" color="white" frame="true" align="right" spinBox="true" caption="2c1o, resolution 2.75Å" /> '''ENAIIHIS FAB FRAGME...)
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Revision as of 07:41, 18 November 2007
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ENAIIHIS FAB FRAGMENT IN THE FREE FORM
Overview
Enantioselective antibodies can separate the enantiomers of a chiral, compound in a highly specific manner. We have recently reported the, cloning and applications of a recombinant Fab-fragment, ENA11His, in the, enantioseparation of a drug candidate, finrozole, which contains two, chiral centers. Here, the crystal structures of this enantioselective, antibody Fab-fragment are determined in the absence of the hapten at a, resolution of 2.75 A, and in the presence of the hapten at 2.05 A, resolution. The conformation of the protein was found to be similar in, both free and complex forms. The hapten molecule was tightly bound in a, deep cleft between the light and heavy chains of the Fab-fragment. The, complex structure also allowed us to describe the molecular basis for, enantioselectivity and to deduce the absolute configurations of all the, four different stereoisomers (a-d) of finrozole. The ENA11His antibody, fragment selectively binds the SR (a) enantiomer from the racemic mixture, of a and d-enantiomers, thus allowing separation from the, pharmacologically most active RS enantiomer (d). In particular, Asp95 and, Asn35 of the H-chain in the ENA11 His antibody seem to provide this, specificity through hydrogen bonding.
About this Structure
2C1O is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structures of an enantioselective fab-fragment in free and complex forms., Parkkinen T, Nevanen TK, Koivula A, Rouvinen J, J Mol Biol. 2006 Mar 24;357(2):471-80. Epub 2006 Jan 3. PMID:16427081
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