|
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
Crystal Structure of Human Pirin
AN IRON-BINDING NUCLEAR PROTEIN AND TRANSCRIPTION COFACTOR*
Hai Pang ,
Mark Bartlam ,
Qinghong Zeng ,
Hideyuki Miyatake¶,
Tamao Hisano¶,
Kunio Miki¶,
Luet-Lok Wong||,
George F. Gao **, and
Zihe Rao 
From the
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 -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- 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.
 To whom correspondence should be addressed. Tel.: 86-010-6277-1493; Fax: 86-010-6277-3145; E-mail: raozh{at}xtal.tsinghua.edu.cn.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. F. J. Bassetti, J. White, J. W. Kappler, and P. Marrack
Transgenic Bcl-3 slows T cell proliferation
Int. Immunol.,
April 1, 2009;
21(4):
339 - 348.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. C. Kim, W. S. Chung, D.-J. Yun, and M. J. Cho
Calcium and Calmodulin-Mediated Regulation of Gene Expression in Plants
Mol Plant,
January 6, 2009;
(2009)
ssn091v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. M. Warpeha, S. Upadhyay, J. Yeh, J. Adamiak, S. I. Hawkins, Y. R. Lapik, M. B. Anderson, and L. S. Kaufman
The GCR1, GPA1, PRN1, NF-Y Signal Chain Mediates Both Blue Light and Abscisic Acid Responses in Arabidopsis
Plant Physiology,
April 1, 2007;
143(4):
1590 - 1600.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Ye, X. Wu, L. Wei, D. Tang, P. Sun, M. Bartlam, and Z. Rao
An Insight into the Mechanism of Human Cysteine Dioxygenase: KEY ROLES OF THE THIOETHER-BONDED TYROSINE-CYSTEINE COFACTOR
J. Biol. Chem.,
February 2, 2007;
282(5):
3391 - 3402.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P.-C. Soo, Y.-T. Horng, M.-J. Lai, J.-R. Wei, S.-C. Hsieh, Y.-L. Chang, Y.-H. Tsai, and H.-C. Lai
Pirin Regulates Pyruvate Catabolism by Interacting with the Pyruvate Dehydrogenase E1 Subunit and Modulating Pyruvate Dehydrogenase Activity
J. Bacteriol.,
January 1, 2007;
189(1):
109 - 118.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. M. Warpeha, S. S. Lateef, Y. Lapik, M. Anderson, B.-S. Lee, and L. S. Kaufman
G-Protein-Coupled Receptor 1, G-Protein G{alpha}-Subunit 1, and Prephenate Dehydratase 1 Are Required for Blue Light-Induced Production of Phenylalanine in Etiolated Arabidopsis
Plant Physiology,
March 1, 2006;
140(3):
844 - 855.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Adams and Z. Jia
Structural and Biochemical Analysis Reveal Pirins to Possess Quercetinase Activity
J. Biol. Chem.,
August 5, 2005;
280(31):
28675 - 28682.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Bunda, N. Kaviani, and A. Hinek
Fluctuations of Intracellular Iron Modulate Elastin Production
J. Biol. Chem.,
January 21, 2005;
280(3):
2341 - 2351.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|