Activation mechanisms of clinically distinct B-Raf V600Eand V600K mutants

作     者：Mingzhen Zhang Ryan Maloney Yonglan Liu Hyunbum Jang Ruth Nussinov 

作者机构：Computational Structural Biology SectionFrederick National Laboratory for Cancer ResearchFrederickMDU.S.A. Cancer Innovation LaboratoryNational Cancer InstituteFrederickMDU.S.A. Department of Human Molecular Genetics and BiochemistrySackler School of MedicineTel Aviv UniversityTel AvivIsrael 

出 版 物：《Cancer Communications》 (癌症通讯（英文）)

年 卷 期：2023年第43卷第3期

页      面：405-408页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the National Cancer Institute National Institutes of Health under contract HHSN261201500003I 

主　　题：V600E V600 melanoma 

摘      要：Dear Editor,B-Raf,the main effector of Ras in the mitogen-activated protein kinase(MAPK)pathway,is among the most highly mutated kinases in human cancer[1].About 40%-60%of melanoma patients harbor B-Raf mutations,of which∼90%involve V600E and V600K.B-RafV600E is more frequent(60%-80%)than B-RafV600K(10%-30%).Substitution of a Val codon by Glu requires a single nucleotide change,whereas Val to Lys requires two[2].This is in line with melanoma patients harboring the V600K mutation,who usually suffer from higher sun exposure that may induce increased DNA damage[3].Since both mutations occur at the same position of the kinase domain and are mutated to charged residues,it was believed that the B-Raf V600E and V600K mutantswould share a similar behavior,and in clinical trials,patients with V600E and V600K mutations have been recruited into the same cohort.