2c1o
From Proteopedia
(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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| - | [[Image:2c1o.gif|left|200px]]<br /> | + | [[Image:2c1o.gif|left|200px]]<br /><applet load="2c1o" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2c1o" size=" | + | |
caption="2c1o, resolution 2.75Å" /> | caption="2c1o, resolution 2.75Å" /> | ||
'''ENAIIHIS FAB FRAGMENT IN THE FREE FORM'''<br /> | '''ENAIIHIS FAB FRAGMENT IN THE FREE FORM'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Enantioselective antibodies can separate the enantiomers of a chiral | + | 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== | ==About this Structure== | ||
| - | 2C1O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 2C1O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C1O OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Koivula, A.]] | [[Category: Koivula, A.]] | ||
| - | [[Category: Nevanen, T | + | [[Category: Nevanen, T K.]] |
[[Category: Parkkinen, T.]] | [[Category: Parkkinen, T.]] | ||
[[Category: Rouvinen, J.]] | [[Category: Rouvinen, J.]] | ||
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[[Category: immunoglobulin domain]] | [[Category: immunoglobulin domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:43:54 2008'' |
Revision as of 14:43, 21 February 2008
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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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