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rdf:type |
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lifeskim:mentions |
umls-concept:C0008810,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0040649,
umls-concept:C0205409,
umls-concept:C0220905,
umls-concept:C0332281,
umls-concept:C1418465,
umls-concept:C1514562,
umls-concept:C1521761,
umls-concept:C1521970,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
23
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pubmed:dateCreated |
2008-6-3
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pubmed:abstractText |
Neuronal PAS protein 2 (NPAS2), a heme-binding transcriptional regulatory factor, is involved in circadian rhythms. Period homologue (Per) is another important transcriptional regulatory factor that binds to cryptochrome (Cry). The resultant Per/Cry heterodimer interacts with the NPAS2/BMAL1 heterodimer to inhibit the transcription of Per and Cry. Previous cell biology experiments indicate that mouse Per2 (mPer2) is also a heme-binding protein, and heme shuttling between mPer2 and NPAS2 may regulate transcription. In the present study, we show that the isolated PAS-A domain of mPer2 (PAS-A-mPer2) binds the Fe(III) protoporphyrin IX complex (hemin) with a heme:protein stoichiometry of 1:1. Optical absorption and EPR spectroscopic findings suggest that the Fe(III)-bound PAS-A-mPer2 is a six-coordinated low-spin complex with Cys and an unknown axial ligand. A Hg (2+) binding study supports the theory that Cys is one of the axial ligands for Fe(III)-bound PAS-A-mPer2. The dissociation rate constant of the Fe(III) complex from PAS-A-mPer2 (6.3 x 10 (-4) s (-1)) was comparable to that of the heme-regulated inhibitor (HRI), a heme-sensor enzyme (1.5 x 10 (-3) s (-1)), but markedly higher than that of metmyoglobin (8.4 x 10 (-7) s (-1)). As confirmed by a Soret absorption spectral shift, heme transferred from the holo basic helix-loop-helix PAS-A of NPAS2 to apoPAS-A-mPer2. The Soret CD spectrum of the C215A mutant PAS-A-mPer2 protein was markedly different from that of the wild-type protein. On the basis of the data, we propose that PAS-A-mPer2 is a heme-sensor protein in which Cys215 is the heme axial ligand.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Heme,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/Mercury,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Npas2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Per2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Period Circadian Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1520-4995
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6157-68
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18479150-Animals,
pubmed-meshheading:18479150-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:18479150-Binding Sites,
pubmed-meshheading:18479150-Brain,
pubmed-meshheading:18479150-Cell Cycle Proteins,
pubmed-meshheading:18479150-Circadian Rhythm,
pubmed-meshheading:18479150-Cloning, Molecular,
pubmed-meshheading:18479150-Cysteine,
pubmed-meshheading:18479150-DNA Primers,
pubmed-meshheading:18479150-Heme,
pubmed-meshheading:18479150-Iron,
pubmed-meshheading:18479150-Mercury,
pubmed-meshheading:18479150-Mice,
pubmed-meshheading:18479150-Nerve Tissue Proteins,
pubmed-meshheading:18479150-Nuclear Proteins,
pubmed-meshheading:18479150-Peptide Fragments,
pubmed-meshheading:18479150-Period Circadian Proteins,
pubmed-meshheading:18479150-Recombinant Proteins,
pubmed-meshheading:18479150-Spectrum Analysis, Raman,
pubmed-meshheading:18479150-Transcription Factors
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pubmed:year |
2008
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pubmed:articleTitle |
Heme-binding characteristics of the isolated PAS-A domain of mouse Per2, a transcriptional regulatory factor associated with circadian rhythms.
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pubmed:affiliation |
Institute of Multidisciplinary Research for Advanced Materials, Tohoku UniVersity, Katahira, Sendai 980-8577, Japan.
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pubmed:publicationType |
Journal Article
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