caa a22 4500 475744063 CHVBK 20180406123508.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1023/A:1007127700199 doi (NATIONALLICENCE)springer-10.1023/A:1007127700199 Identification, Using Molecular Dynamics, of an Effector Domain of the ras-Binding Domain of the raf-p74 Protein That Is Uniquely Involved in Oncogenic ras-p21 Signaling [Elektronische Daten] [James Chen, Kiran Rijhwani, Fred Friedman, Mark Hyde, Matthew Pincus] By comparing the average structures, computed using molecular dynamics, of the ras-binding domain of raf (RBD) bound to activated wild-type ras-p21 and its homologous inhibitory protein, rap-1A, we formerly identified three domains of the RBD that changed conformation between the two complexes, residues 62-76, 97-110, and 111-121. We found that one synthetic peptide, corresponding to RBD residues 97-110, selectively inhibited oncogenic ras-p21-induced oocyte maturation. In this study, we performed molecular dynamics on the Val 12-ras-p21-RBD complex and compared its average structure with that for the wild-type protein. We find that there is a large displacement of a loop involving these residues when the structures of the two complexes are compared. This result corroborates our former finding that the RBD 97-110 peptide inhibits only signal transduction by oncogenic ras-p21 and suggests that oncogenic p21 uses this loop to interact with raf in a unique manner. Plenum Publishing Corporation, 2000 ras -p21-RBD complex nationallicence molecular dynamics nationallicence average structure nationallicence effector domains nationallicence 97-110 RBD PNC-13 peptide nationallicence Chen James Tularik, Inc., 94080, South San Francisco, California aut Rijhwani Kiran Department of Pathology and Laboratory Medicine, Harbor VA Medical Center, 800 Doly Place, 11209, Brooklyn, New York aut Friedman Fred Laboratory of Metabolism, NCI, National Institutes of Health, 20892, Bethesda, Maryland aut Hyde Mark Advanced Computing Services, 13214, DeWitt, New York aut Pincus Matthew Department of Pathology and Laboratory Medicine, Harbor VA Medical Center, 800 Doly Place, 11209, Brooklyn, New York aut Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/7(2000-10-01), 545-551 0277-8033 19:7<545 2000 19 10930 https://doi.org/10.1023/A:1007127700199 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007127700199 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen James Tularik, Inc., 94080, South San Francisco, California aut NATIONALLICENCE 700 1- Rijhwani Kiran Department of Pathology and Laboratory Medicine, Harbor VA Medical Center, 800 Doly Place, 11209, Brooklyn, New York aut NATIONALLICENCE 700 1- Friedman Fred Laboratory of Metabolism, NCI, National Institutes of Health, 20892, Bethesda, Maryland aut NATIONALLICENCE 700 1- Hyde Mark Advanced Computing Services, 13214, DeWitt, New York aut NATIONALLICENCE 700 1- Pincus Matthew Department of Pathology and Laboratory Medicine, Harbor VA Medical Center, 800 Doly Place, 11209, Brooklyn, New York aut NATIONALLICENCE 773 0- Journal of Protein Chemistry Kluwer Academic Publishers-Plenum Publishers 19/7(2000-10-01), 545-551 0277-8033 19:7<545 2000 19 10930 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer