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Maria C. Bewley
Biology Department, 463
tel: (631) 344-3798
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Research Interests:
My laboratory is interested in structure/function analysis of multicomponent enzymatic pathways. Our understanding of the function of such pathways is often incomplete because typically individual proteins have been studied in isolation rather than in the context of a biologically relevant complex. There are two systems that I am focusing on; the primary system is the pathway by which DNA double strand break (DSB) repair occurs in mammalian cells and the secondary system is the electron transfer pathway of fatty acid biosynthesis. DSB repair is crucial to the survival of a cell, yet its mechanism is relatively poorly understood. It is known that protein:protein interactions play a crucial part in the regulation and action of repair, and some of the players are already known including DNA protein kinase (DNA-PK), Ku70:80, XRCC4 and DNA ligase IV. Fatty acid desaturation occurs in all mammals and involves the transfer of electrons from b5 reductase(B5R)-bound NADH to cytochrome b5. How this transfer is achieved is one of the key unanswered questions in this pathway. My research centers on obtaining their structures, alone, and in biologically relevant complexes. |
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Publications:
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MacGillivray, R.T.A., Bewley, M.C., Smith, C.A., He, Q.Y., Mason, A.B.,
Woodworth, R.C. and Baker, E.N. Mutation of the iron ligand His249 to Glu in the N-lobe of human transferrin abolishes the dilysine 'trigger' but does not significantly affect iron release. Biochem. 39, 1211-1216 (2000). Medline Abstract PDB file 1DTG |
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Bewley, M.C., Springer, K., Zhang, Y.-B., Freimuth, P., and Flanagan, J.M. Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. Science, 286, 1579-1583 (1999). Medline Abstract , Full Text (pdf) PDB files 1KAC, 1NOB |
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Bewley, M.C., Jeffrey, P.D., Patchett, M.L., Kanyo, Z.F., and Baker, E.N. Crystal structures of Bacillus caldovelox arginase in complex with substrate and inhibitors reveal new insights into activation, inhibition and catalysis in the arginase superfamily. Structure 7, 435-448 (1999). Medline Abstract PDB files 1CEV, 2CEV, 3CEV, 4CEV, 5CEV |
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Bewley, M.C., Tam, B.M., Grewal, J., He, S., Shewry, S., Murphy, M.E.,
Mason, A.B., Woodworth, R.C., Baker, E.N., and MacGillivray, R.T. X-ray crystallography and mass spectroscopy reveal that the N-lobe of human transferrin expressed in Pichia pastoris is folded correctly but is glycosylated on serine-32. Biochemistry 38, 2535-2541 (1999). Medline Abstract PDB file 1B3E |
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Freimuth, P., Springer, K., Berard, C., Hainfeld, J., Bewley, M.,
and Flanagan, J. Coxsackievirus and adenovirus receptor amino-terminal immunoglobulin V related domain binds adenovirus type 2 and fiber knob from adenovirus type 12. J. Virol. 73, 1392-1398 (1999). Medline Abstract , Full Text (pdf) |
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Qin, B.Y., Bewley, M.C., Creamer, L.K., Baker, E.N., and Jameson, G.B. Functional implications of structural differences between variants A and B of bovine beta-lactoglobulin. Protein Sci. 8, 75-83 (1999). Medline Abstract PDB file 1BSQ |
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Qin, B.Y., Bewley, M.C., Creamer, L.K., Baker, H.M., Baker, E.N.,
and Jameson, G.B. Structural basis of the Tanford transition of bovine beta-lactoglobulin. Biochemistry 37, 14014-14023 (1998). Medline Abstract PDB files 1BSY, 2BLG, 3BLG |
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Jeffrey, P.D., Bewley, M.C., MacGillivray, R.T., Mason, A., Woodworth, R.,
and Baker, E.N. Ligand-induced conformational change in transferrins: crystal structure of the open form of the N-terminal half-molecule of human transferrin. Biochemistry 37, 13978-13986 (1998). Medline Abstract PDB files 1BP5, 1BTJ |
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Bewley, M.C., Qin, B.Y., Jameson, G.B., Sawyer, L., and Baker, E.N. Bovine P-lactoglobulin and its variants: A three dimensional perspective. In: Milk Protein Polymorphism, Int. Fed. Bull. Special Issue. IDF: Brussels, pp. 101-109 (1998). |
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MacGillivray, R.T., Moore, S.A., Chen, J., Anderson, B.F., Baker, H.,
Luo, Y., Bewley, M., Smith, C.A., Murphy, M.E., Wang, Y., Mason, A.B.,
Woodworth, R.C., Brayer, G.D., and Baker, E.N. Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release. Biochemistry 37, 7919-7928 (1998). Medline Abstract PDB files 1A8F, 1A8E |
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Attwood, T.K., Avison, H., Beck, M.E., Bewley, M., Bleasby, A.J.,
Brewster, F., Cooper, P., Degtyarenko, K., Geddes, A.J., Flower, D.R.,
Kelly, M.P., Lott, S., Measures, K.M., Parry-Smith, D.J., Perkins, D.N.,
Scordis, P., Scott, D., and Worledge, C. The PRINTS database of protein fingerprints: A novel information resource for computational molecular biology. J. Chem. Inf. Comput. Sci. 37, 417-424 (1997). Medline Abstract |
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Bewley, M.C., Lott, J.S., Baker, E.N., and Patchett, M.L. The cloning, expression, and crystallization of a thermostable arginase. FEBS Letts. 386, 215-218 (1996). Medline Abstract |
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Holzenberg, A., Bewley, M.C., Wilson, F.H., Nicholson, W.V., and Ford, R.C. Three dimensional structure of photosystem II. Nature 363, 470-472 (1993). |
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Bewley, M.C., Boustead, C.M., Walker, J.H., Waller, D.A., and Huber, R. Structure of chicken annexin V at 2.25 A resolution. Biochemistry 32, 3923-3929 (1993). Medline Abstract PDB file 1ALA |
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Walker, J.H., Boustead, C.M., Koster, J.J., Bewley, M., and Waller, D.A. Annexin V, a calcium dependent phospholipid-binding protein. Biochem. Soc. Trans. 20, 828-833 (1992). Medline Reference |
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