6L8U

Crystal structure of human BCDIN3D in complex with SAH

6L8U の概要

• エントリーDOI: 10.2210/pdb6l8u/pdb
• 分子名称: RNA 5'-monophosphate methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• 機能のキーワード: methyltransferase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 131343.10

構造登録者

Liu, Y.,Martinez, A.,Yamashita, S.,Tomita, K. (登録日: 2019-11-07, 公開日: 2019-12-25, 最終更新日: 2023-11-22)

主引用文献

Liu, Y.,Martinez, A.,Yamashita, S.,Tomita, K.
Crystal structure of human cytoplasmic tRNAHis-specific 5'-monomethylphosphate capping enzyme.
Nucleic Acids Res., 48:1572-1582, 2020

PubMed Abstract: BCDIN3 domain containing RNA methyltransferase, BCDIN3D, monomethylates the 5'-monophosphate of cytoplasmic tRNAHis with a G-1:A73 mispair at the top of an eight-nucleotide-long acceptor helix, using S-adenosyl-l-methionine (SAM) as a methyl group donor. In humans, BCDIN3D overexpression is associated with the tumorigenic phenotype and poor prognosis in breast cancer. Here, we present the crystal structure of human BCDIN3D complexed with S-adenosyl-l-homocysteine. BCDIN3D adopts a classical Rossmann-fold methyltransferase structure. A comparison of the structure with that of the closely related methylphosphate capping enzyme, MePCE, which monomethylates the 5'-γ-phosphate of 7SK RNA, revealed the important residues for monomethyl transfer from SAM onto the 5'-monophosphate of tRNAHis and for tRNAHis recognition by BCDIN3D. A structural model of tRNAHis docking onto BCDIN3D suggested the molecular mechanism underlying the different activities between BCDIN3D and MePCE. A loop in BCDIN3D is shorter, as compared to the corresponding region that forms an α-helix to recognize the 5'-end of RNA in MePCE, and the G-1:A73 mispair in tRNAHis allows the N-terminal α-helix of BCDIN3D to wedge the G-1:A73 mispair of tRNAHis. As a result, the 5'-monophosphate of G-1 of tRNAHis is deep in the catalytic pocket for 5'-phosphate methylation. Thus, BCDIN3D is a tRNAHis-specific 5'-monomethylphosphate capping enzyme that discriminates tRNAHis from other tRNA species, and the structural information presented in this study also provides the molecular basis for the development of drugs against breast cancers.

PubMed: 31919512
DOI: 10.1093/nar/gkz1216

実験手法

X-RAY DIFFRACTION (2.925 Å)