32c2

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{{STRUCTURE_32c2| PDB=32c2 | SCENE= }}
{{STRUCTURE_32c2| PDB=32c2 | SCENE= }}
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'''STRUCTURE OF AN ACTIVITY SUPPRESSING FAB FRAGMENT TO CYTOCHROME P450 AROMATASE'''
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===STRUCTURE OF AN ACTIVITY SUPPRESSING FAB FRAGMENT TO CYTOCHROME P450 AROMATASE===
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==Overview==
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The crystal structure of a Fab fragment (Fab3-2C2) of a monoclonal antibody raised against aromatase cytochrome P450 P450arom) has been determined at 3.0 A resolution. P450arom is a membrane bound enzyme responsible for the catalysis of indrogens to estrogens, the process of aromatization, and hence has been implicated in hormone-dependent breast cancer. The Fab fragment of MAb3-2C2 IgG suppresses P450arom activity in a dose dependent manner. The Fab3-2C2 molecule crystallizes n the space group P2(1)2(1)2(1) with a unit cell of a= 154.89 A, b = 73.51 A, and c= 36.90 A. The crystal structure consists of a light and a heavy chain in the asymmetric unit, each characterized by the greek-key antiparallel beta barrel folding seen in all Fab structures. The average elbow angle between the two domains is 143 degrees. Modeling of the interactions between the variable domains of the antibody and a known model of P450arom maps the epitope to a region of the enzyme that is consistent with the available biochemical data and the activity-suppressing function of the antibody. The epitope mapping result is further supported by the inability of MAb3-2C2 IgG to suppress the activity of, or to interact with placental porcine P450arom, which is 81% identical (86% similar) to human P450arom but has a few key substitutions in the putative epitope region.
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==About this Structure==
==About this Structure==
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[[Category: Fab]]
[[Category: Fab]]
[[Category: P450]]
[[Category: P450]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 10:49:43 2008''

Revision as of 07:49, 29 July 2008

Template:STRUCTURE 32c2

STRUCTURE OF AN ACTIVITY SUPPRESSING FAB FRAGMENT TO CYTOCHROME P450 AROMATASE

Template:ABSTRACT PUBMED 10449095

About this Structure

Full crystallographic information is available from OCA.

Reference

Structure of an activity suppressing Fab fragment to cytochrome P450 aromatase: insights into the antibody-antigen interactions., Sawicki MW, Ng PC, Burkhart BM, Pletnev VZ, Higashiyama T, Osawa Y, Ghosh D, Mol Immunol. 1999 May;36(7):423-32. PMID:10449095

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