Structural basis for substrate recognition by the human N-terminal methyltransferase 1 [electronic resource]

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 541 Physical chemistry

Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015

Mô tả vật lý: Size: p. 2343-2348 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 261379

?-N-terminal methylation represents a highly conserved and prevalent post-translational modification, yet its biological function has remained largely speculative. The recent discovery of ?-N-terminal methyltransferase 1 (NTMT1) and its physiological substrates propels the elucidation of a general role of ?-N-terminal methylation in mediating DNA-binding ability of the modified proteins. The phenotypes, observed from both NTMT1 knockdown in breast cancer cell lines and knockout mouse models, suggest the potential involvement of ?-N-terminal methylation in DNA damage response and cancer development. In this study, we report the first crystal structures of human NTMT1 in complex with cofactor S-adenosyl-L-homocysteine (SAH) and six substrate peptides, respectively, and reveal that NTMT1 contains two characteristic structural elements (a ? hairpin and an N-terminal extension) that contribute to its substrate specificity. Our complex structures, coupled with mutagenesis, binding, and enzymatic studies, also present the key elements involved in locking the consensus substrate motif XPK (X indicates any residue type other than D/E) into the catalytic pocket for ?-N-terminal methylation and explain why NTMT1 prefers an XPK sequence motif. We propose a catalytic mechanism for ?-N-terminal methylation. Overall, this study gives us the first glimpse of the molecular mechanism of ?-N-terminal methylation and potentially contributes to the advent of therapeutic agents for human diseases associated with deregulated ?-N-terminal methylation.
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 71010608 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH