2riq
From Proteopedia
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==Overview== | ==Overview== | ||
| - | PARP-1 is a chromatin-associated enzyme with multiple cellular functions, including DNA repair, transcriptional regulation, and cell signaling. | + | Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme with multiple cellular functions, including DNA repair, transcriptional regulation, and cell signaling. PARP-1 has a modular architecture with six independent domains comprising the 113-kDa polypeptide. Two zinc finger domains at the N terminus of PARP-1 bind to DNA and thereby activate the catalytic domain situated at the C terminus of the enzyme. The tight coupling of DNA binding and catalytic activities is critical to the cellular regulation of PARP-1 function; however, the mechanism for coordinating these activities remains an unsolved problem. Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. Biochemical mutagenesis and deletion analysis indicate that this region mediates interdomain contacts important for DNA-dependent enzyme activation. The crystal structure of the third zinc-binding domain reveals a zinc ribbon fold and suggests conserved residues that could form interdomain contacts. The new zinc-binding domain self-associates in the crystal lattice to form a homodimer with a head-totail arrangement. The structure of the homodimer provides a scaffold for assembling the activated state of PARP-1 and suggests a mechanism for coupling the DNA binding and catalytic functions of PARP-1. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | A | + | A Third Zinc-binding Domain of Human Poly(ADP-ribose) Polymerase-1 Coordinates DNA-dependent Enzyme Activation., Langelier MF, Servent KM, Rogers EE, Pascal JM, J Biol Chem. 2008 Feb 15;283(7):4105-14. Epub 2007 Nov 30. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18055453 18055453] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: NAD(+) ADP-ribosyltransferase]] | [[Category: NAD(+) ADP-ribosyltransferase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Langelier, M | + | [[Category: Langelier, M F.]] |
| - | [[Category: Pascal, J | + | [[Category: Pascal, J M.]] |
| - | [[Category: Servent, K | + | [[Category: Servent, K M.]] |
[[Category: EOH]] | [[Category: EOH]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: zn-binding domain]] | [[Category: zn-binding domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:47:37 2008'' |
Revision as of 16:47, 21 February 2008
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Crystal Structure of the Third Zinc-binding domain of human PARP-1
Overview
Poly(ADP-ribose) polymerase-1 (PARP-1) is a chromatin-associated enzyme with multiple cellular functions, including DNA repair, transcriptional regulation, and cell signaling. PARP-1 has a modular architecture with six independent domains comprising the 113-kDa polypeptide. Two zinc finger domains at the N terminus of PARP-1 bind to DNA and thereby activate the catalytic domain situated at the C terminus of the enzyme. The tight coupling of DNA binding and catalytic activities is critical to the cellular regulation of PARP-1 function; however, the mechanism for coordinating these activities remains an unsolved problem. Here, we demonstrate using spectroscopic and crystallographic analysis that human PARP-1 has a third zinc-binding domain. Biochemical mutagenesis and deletion analysis indicate that this region mediates interdomain contacts important for DNA-dependent enzyme activation. The crystal structure of the third zinc-binding domain reveals a zinc ribbon fold and suggests conserved residues that could form interdomain contacts. The new zinc-binding domain self-associates in the crystal lattice to form a homodimer with a head-totail arrangement. The structure of the homodimer provides a scaffold for assembling the activated state of PARP-1 and suggests a mechanism for coupling the DNA binding and catalytic functions of PARP-1.
About this Structure
2RIQ is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Known structural/functional Sites: , , , and . Full crystallographic information is available from OCA.
Reference
A Third Zinc-binding Domain of Human Poly(ADP-ribose) Polymerase-1 Coordinates DNA-dependent Enzyme Activation., Langelier MF, Servent KM, Rogers EE, Pascal JM, J Biol Chem. 2008 Feb 15;283(7):4105-14. Epub 2007 Nov 30. PMID:18055453
Page seeded by OCA on Thu Feb 21 18:47:37 2008
Categories: Homo sapiens | NAD(+) ADP-ribosyltransferase | Single protein | Langelier, M F. | Pascal, J M. | Servent, K M. | EOH | GOL | ZN | Adp-ribosylation | Dna damage | Dna repair | Dna-binding | Glycosyltransferase | Metal-binding | Nad | Nucleus | Phosphorylation | Polymorphism | Transferase | Zinc | Zinc-finger | Zn finger | Zn ribbon | Zn-binding domain
