32C2

STRUCTURE OF AN ACTIVITY SUPPRESSING FAB FRAGMENT TO CYTOCHROME P450 AROMATASE

32C2 の概要

• エントリーDOI: 10.2210/pdb32c2/pdb
• 分子名称: IGG1 ANTIBODY 32C2 (2 entities in total)
• 機能のキーワード: fab, antibody, aromatase, p450, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47295.49

構造登録者

Sawicki, M.W.,Ng, P.C.,Burkhart, B.,Pletnev, V.,Higashiyama, T.,Osawa, Y.,Ghosh, D. (登録日: 1999-04-21, 公開日: 2000-04-26, 最終更新日: 2024-10-16)

主引用文献

Sawicki, M.W.,Ng, P.C.,Burkhart, B.M.,Pletnev, V.Z.,Higashiyama, T.,Osawa, Y.,Ghosh, D.
Structure of an activity suppressing Fab fragment to cytochrome P450 aromatase: insights into the antibody-antigen interactions.
Mol.Immunol., 36:423-432, 1999

PubMed Abstract: 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.

PubMed: 10449095
DOI: 10.1016/S0161-5890(99)00062-0

実験手法

X-RAY DIFFRACTION (3 Å)