2jnw: Difference between revisions
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New page: left|200px<br /> <applet load="2jnw" size="450" color="white" frame="true" align="right" spinBox="true" caption="2jnw" /> '''Solution structure of a ERCC1-XPA heterodim... |
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[[Image:2jnw.gif|left|200px]]<br /> | [[Image:2jnw.gif|left|200px]]<br /><applet load="2jnw" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Solution structure of a ERCC1-XPA heterodimer'''<br /> | '''Solution structure of a ERCC1-XPA heterodimer'''<br /> | ||
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==Overview== | ==Overview== | ||
The nucleotide excision repair (NER) pathway corrects DNA damage caused by, sunlight, environmental mutagens and certain antitumor agents. This, multistep DNA repair reaction operates by the sequential assembly of, protein factors at sites of DNA damage. The efficient recognition of DNA, damage and its repair are orchestrated by specific protein-protein and, protein-DNA interactions within NER complexes. We have investigated an, essential protein-protein interaction of the NER pathway, the binding of, the XPA protein to the ERCC1 subunit of the repair endonuclease ERCC1-XPF., The structure of ERCC1 in complex with an XPA peptide shows that only a, small region of XPA interacts with ERCC1 to form a stable complex, exhibiting submicromolar binding affinity. However, this XPA peptide is a, potent inhibitor of NER activity in a cell-free assay, blocking the, excision of a cisplatin adduct from DNA. The structure of the peptide, inhibitor bound to its target site reveals a binding interface that is, amenable to the development of small molecule peptidomimetics that could, be used to modulate NER repair activities in vivo. | The nucleotide excision repair (NER) pathway corrects DNA damage caused by, sunlight, environmental mutagens and certain antitumor agents. This, multistep DNA repair reaction operates by the sequential assembly of, protein factors at sites of DNA damage. The efficient recognition of DNA, damage and its repair are orchestrated by specific protein-protein and, protein-DNA interactions within NER complexes. We have investigated an, essential protein-protein interaction of the NER pathway, the binding of, the XPA protein to the ERCC1 subunit of the repair endonuclease ERCC1-XPF., The structure of ERCC1 in complex with an XPA peptide shows that only a, small region of XPA interacts with ERCC1 to form a stable complex, exhibiting submicromolar binding affinity. However, this XPA peptide is a, potent inhibitor of NER activity in a cell-free assay, blocking the, excision of a cisplatin adduct from DNA. The structure of the peptide, inhibitor bound to its target site reveals a binding interface that is, amenable to the development of small molecule peptidomimetics that could, be used to modulate NER repair activities in vivo. | ||
==About this Structure== | ==About this Structure== | ||
2JNW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 2JNW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JNW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: xpa]] | [[Category: xpa]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:56:54 2008'' | ||
