Design, synthesis, and characterization of BRC4 mutants based on the crystal structure of BRC4-RAD51(191-220)

Verfasser / Beitragende:
[Dongxin Zhao, Kui Lu]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Molecular Modeling, 21/11(2015-11-01), 1-7
Format:
Artikel (online)
ID: 605513619
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024 7 0 |a 10.1007/s00894-015-2831-x  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00894-015-2831-x 
245 0 0 |a Design, synthesis, and characterization of BRC4 mutants based on the crystal structure of BRC4-RAD51(191-220)  |h [Elektronische Daten]  |c [Dongxin Zhao, Kui Lu] 
520 3 |a Breast cancer susceptibility gene 2 (BRCA2)—a human tumor suppressor gene—is related to various malignancies such as breast and ovarian cancer. This gene can induce the key protein RAD51 recombinase, which is involved in homologous recombination with single-stranded DNA in the human body and can regulate RAD51 to complete the repair of damaged double-stranded DNA. Eight highly conserved BRC repeat motifs in BRCA2 protein serve as sites for the interaction between BRCA2 and RAD51. BRCA2 regulates RAD51 through these motifs. However, the mechanism of this interaction still requires further research. In this study, the BRC4 motif that demonstrated strong interaction with RAD51 was selected as template peptide. On the basis of known data regarding the crystal structure of the BRC4-RAD51(191-220) complex, a series of BRC4 mutants was designed using PyMOL software based on the sequence of BRC4, and polypeptides were synthesized by the Fmoc solid-phase method. After purification by reversed-phase high-performance liquid chromatography, the purity of the polypeptides reached >95%. The primary determination of circular dichroism spectra showed that the polypeptides exhibited slight changes in secondary structure, which indicated that mutation on the non-conserved sites in BRC4 probably affected the interaction with BRC4. These findings will facilitate research on the interaction between targeting peptides and BRC4 mutants, as well the basic rules covering this interaction. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a BRC4  |2 nationallicence 
690 7 |a Peptide synthesis  |2 nationallicence 
690 7 |a Mutant  |2 nationallicence 
690 7 |a Structure  |2 nationallicence 
690 7 |a Stimulation  |2 nationallicence 
700 1 |a Zhao  |D Dongxin  |u School of Chemistry and Chemical Engineering, Henan University of Technology, 450001, Zhengzhou, China  |4 aut 
700 1 |a Lu  |D Kui  |u School of Chemistry and Chemical Engineering, Henan University of Technology, 450001, Zhengzhou, China  |4 aut 
773 0 |t Journal of Molecular Modeling  |d Springer Berlin Heidelberg  |g 21/11(2015-11-01), 1-7  |x 1610-2940  |q 21:11<1  |1 2015  |2 21  |o 894 
856 4 0 |u https://doi.org/10.1007/s00894-015-2831-x  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00894-015-2831-x  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhao  |D Dongxin  |u School of Chemistry and Chemical Engineering, Henan University of Technology, 450001, Zhengzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lu  |D Kui  |u School of Chemistry and Chemical Engineering, Henan University of Technology, 450001, Zhengzhou, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Molecular Modeling  |d Springer Berlin Heidelberg  |g 21/11(2015-11-01), 1-7  |x 1610-2940  |q 21:11<1  |1 2015  |2 21  |o 894