Structural highlights
Publication Abstract from PubMed
BAP1 is an apurinic/apyrimidinic lyase (AP lyase) that plays an important role in the repair of DNA damage. The present study deals with the prediction of the 3D structure of bovine AP lyase based on its sequence homology with human AP lyase. The predicted 3D model of bovine AP1 shows remarkable similarity with human endonuclease in the overall 3D fold. However, significant differences in the model and the X-ray structure were located at some of the important sites. We have analyzed the active center of the enzyme and other sites that are involved in DNA repair. A number of amino acids bind the bases located in the major/minor grooves of DNA. An insertion of Arg176 in the major groove and Met270 in the minor groove caps the DNA bound enzyme's active site, stabilizing the extra helical AP site conformation and effectively locking the protein onto the AP-DNA. Three BAP1 mutants were also modeled and analyzed as regards the changes in the structure. Substitution of Arg176-->Ala leads to the loss of DNA binding whereas mutation of Asp282-->Ala and His308-->Asn leads to a decrease in the enzymatic activity.
Three-dimensional structure prediction of bovine AP lyase, BAP1: prediction of interaction with DNA and alterations as a result of Arg176-->Ala, Asp282-->Ala, and His308-->Asn mutations.,Khurshid R, Salim A, Abbasi A Biochem Biophys Res Commun. 2005 Jan 28;326(4):711-7. PMID:15607727[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Khurshid R, Salim A, Abbasi A. Three-dimensional structure prediction of bovine AP lyase, BAP1: prediction of interaction with DNA and alterations as a result of Arg176-->Ala, Asp282-->Ala, and His308-->Asn mutations. Biochem Biophys Res Commun. 2005 Jan 28;326(4):711-7. PMID:15607727 doi:10.1016/j.bbrc.2004.11.103
