2jnw
From Proteopedia
Solution structure of a ERCC1-XPA heterodimer
Structural highlights
DiseaseERCC1_HUMAN Defects in ERCC1 are the cause of cerebro-oculo-facio-skeletal syndrome type 4 (COFS4) [MIM:610758. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.[1] FunctionERCC1_HUMAN Structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA.,Tsodikov OV, Ivanov D, Orelli B, Staresincic L, Shoshani I, Oberman R, Scharer OD, Wagner G, Ellenberger T EMBO J. 2007 Nov 14;26(22):4768-76. Epub 2007 Oct 18. PMID:17948053[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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