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Originally published In Press as doi:10.1074/jbc.M310022200 on October 22, 2003

J. Biol. Chem., Vol. 279, Issue 2, 1491-1498, January 9, 2004
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Crystal Structure of Human Pirin

AN IRON-BINDING NUCLEAR PROTEIN AND TRANSCRIPTION COFACTOR*

Hai Pang{ddagger}§, Mark Bartlam{ddagger}§, Qinghong Zeng{ddagger}§, Hideyuki Miyatake¶, Tamao Hisano¶, Kunio Miki¶, Luet-Lok Wong||, George F. Gao{ddagger}**, and Zihe Rao{ddagger}{ddagger}{ddagger}

From the {ddagger}Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, School of Life Sciences and Engineering, Beijing, Beijing 100084, China, the Theoretical Structural Biology Laboratory, RIKEN Harima Institute, SPring-8, Hyogo 679-5148, Japan, the ||Department of Chemistry, Inorganic Chemistry Laboratory, South Parks Road, Oxford OX1 3QR, United Kingdom, and the **Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom

Pirin is a newly identified nuclear protein that interacts with the oncoprotein B-cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure of human Pirin at 2.1-Å resolution shows it to be a member of the functionally diverse cupin superfamily. The structure comprises two {beta}-barrel domains, with an Fe(II) cofactor bound within the cavity of the N-terminal domain. These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-{kappa}B transcription pathway and the interaction with NFI in DNA replication. Substitution of iron by heavy metals thus provides a novel pathway for these metals to directly influence gene transcription. The structure suggests an interesting new role of iron in biology and that Pirin may be involved in novel mechanisms of gene regulation.


Received for publication, September 9, 2003 , and in revised form, October 13, 2003.

The atomic coordinates and structure factors (code 1J1L) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

* This work was supported by Grants G1999075600 (Project 973) and 2002BA711A12 (Ministry of Science and Technology, China) for the Human Structural Genomics Initiative. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ These authors contributed equally to this work.

{ddagger}{ddagger} To whom correspondence should be addressed. Tel.: 86-010-6277-1493; Fax: 86-010-6277-3145; E-mail: raozh{at}xtal.tsinghua.edu.cn.


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