6MON

Crystal structure of human SMYD2 in complex with Nle-peptide inhibitor

6MON の概要

• エントリーDOI: 10.2210/pdb6mon/pdb
• 分子名称: N-lysine methyltransferase SMYD2, LYS-LEU-NLE-SER-LYS-ARG-GLY, ZINC ION, ... (6 entities in total)
• 機能のキーワード: methyltransferase, norleucine, complex, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 101548.56

構造登録者

Spellmon, N.,Cornett, E.,Brunzelle, J.,Rothbart, S.,Yang, Z. (登録日: 2018-10-04, 公開日: 2018-12-12, 最終更新日: 2023-11-15)

主引用文献

Cornett, E.M.,Dickson, B.M.,Krajewski, K.,Spellmon, N.,Umstead, A.,Vaughan, R.M.,Shaw, K.M.,Versluis, P.P.,Cowles, M.W.,Brunzelle, J.,Yang, Z.,Vega, I.E.,Sun, Z.W.,Rothbart, S.B.
A functional proteomics platform to reveal the sequence determinants of lysine methyltransferase substrate selectivity.
Sci Adv, 4:eaav2623-eaav2623, 2018

PubMed Abstract: Lysine methylation is a key regulator of histone protein function. Beyond histones, few connections have been made to the enzymes responsible for the deposition of these posttranslational modifications. Here, we debut a high-throughput functional proteomics platform that maps the sequence determinants of lysine methyltransferase (KMT) substrate selectivity without a priori knowledge of a substrate or target proteome. We demonstrate the predictive power of this approach for identifying KMT substrates, generating scaffolds for inhibitor design, and predicting the impact of missense mutations on lysine methylation signaling. By comparing KMT selectivity profiles to available lysine methylome datasets, we reveal a disconnect between preferred KMT substrates and the ability to detect these motifs using standard mass spectrometry pipelines. Collectively, our studies validate the use of this platform for guiding the study of lysine methylation signaling and suggest that substantial gaps exist in proteome-wide curation of lysine methylomes.

PubMed: 30498785
DOI: 10.1126/sciadv.aav2623

実験手法

X-RAY DIFFRACTION (2.711 Å)