1h0d

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==Overview==
==Overview==
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The murine monoclonal antibody 26-2F neutralizes the angiogenic and, ribonucleolytic activities of human angiogenin (ANG) and is highly, effective in preventing the establishment and metastatic dissemination of, human tumors in athymic mice. Here we report a 2.0 A resolution crystal, structure for the complex of ANG with the Fab fragment of 26-2F that, reveals the detailed interactions between ANG and the, complementarity-determining regions (CDRs) of the antibody. Surprisingly, Fab binding induces a dramatic conformational change in the cell binding, region of ANG at the opposite end of the molecule from the combining site;, crosslinking experiments indicate that this rearrangement also occurs in, solution. The ANG-Fab complex structure should be invaluable for designing, maximally humanized versions of 26-2F for potential clinical use.
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The murine monoclonal antibody 26-2F neutralizes the angiogenic and ribonucleolytic activities of human angiogenin (ANG) and is highly effective in preventing the establishment and metastatic dissemination of human tumors in athymic mice. Here we report a 2.0 A resolution crystal structure for the complex of ANG with the Fab fragment of 26-2F that reveals the detailed interactions between ANG and the complementarity-determining regions (CDRs) of the antibody. Surprisingly, Fab binding induces a dramatic conformational change in the cell binding region of ANG at the opposite end of the molecule from the combining site; crosslinking experiments indicate that this rearrangement also occurs in solution. The ANG-Fab complex structure should be invaluable for designing maximally humanized versions of 26-2F for potential clinical use.
==Disease==
==Disease==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Acharya, K.R.]]
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[[Category: Acharya, K R.]]
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[[Category: Chavali, G.B.]]
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[[Category: Chavali, G B.]]
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[[Category: Papageorgiou, A.C.]]
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[[Category: Papageorgiou, A C.]]
[[Category: GOL]]
[[Category: GOL]]
[[Category: SO4]]
[[Category: SO4]]
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[[Category: ribonuclease]]
[[Category: ribonuclease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:44:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:56:01 2008''

Revision as of 10:56, 21 February 2008


1h0d, resolution 2.0Å

Drag the structure with the mouse to rotate

CRYSTAL STRUCTURE OF HUMAN ANGIOGENIN IN COMPLEX WITH FAB FRAGMENT OF ITS MONOCLONAL ANTIBODY MAB 26-2F

Contents

Overview

The murine monoclonal antibody 26-2F neutralizes the angiogenic and ribonucleolytic activities of human angiogenin (ANG) and is highly effective in preventing the establishment and metastatic dissemination of human tumors in athymic mice. Here we report a 2.0 A resolution crystal structure for the complex of ANG with the Fab fragment of 26-2F that reveals the detailed interactions between ANG and the complementarity-determining regions (CDRs) of the antibody. Surprisingly, Fab binding induces a dramatic conformational change in the cell binding region of ANG at the opposite end of the molecule from the combining site; crosslinking experiments indicate that this rearrangement also occurs in solution. The ANG-Fab complex structure should be invaluable for designing maximally humanized versions of 26-2F for potential clinical use.

Disease

Known diseases associated with this structure: Amyotrophic lateral sclerosis, susceptibility to OMIM:[105850]

About this Structure

1H0D is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

The crystal structure of human angiogenin in complex with an antitumor neutralizing antibody., Chavali GB, Papageorgiou AC, Olson KA, Fett JW, Hu G, Shapiro R, Acharya KR, Structure. 2003 Jul;11(7):875-85. PMID:12842050

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