5V2N

Crystal Structure of APO Human SETD8

Summary for 5V2N

• Entry DOI: 10.2210/pdb5v2n/pdb
• Descriptor: N-lysine methyltransferase KMT5A, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: methyl transferase, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 18687.02

Authors

Skene, R.J. (deposition date: 2017-03-05, release date: 2018-03-07, Last modification date: 2024-03-06)

Primary citation

Chen, S.,Wiewiora, R.P.,Meng, F.,Babault, N.,Ma, A.,Yu, W.,Qian, K.,Hu, H.,Zou, H.,Wang, J.,Fan, S.,Blum, G.,Pittella-Silva, F.,Beauchamp, K.A.,Tempel, W.,Jiang, H.,Chen, K.,Skene, R.J.,Zheng, Y.G.,Brown, P.J.,Jin, J.,Luo, C.,Chodera, J.D.,Luo, M.
The dynamic conformational landscape of the protein methyltransferase SETD8.
Elife, 8:-, 2019

PubMed Abstract: Elucidating the conformational heterogeneity of proteins is essential for understanding protein function and developing exogenous ligands. With the rapid development of experimental and computational methods, it is of great interest to integrate these approaches to illuminate the conformational landscapes of target proteins. SETD8 is a protein lysine methyltransferase (PKMT), which functions in vivo via the methylation of histone and nonhistone targets. Utilizing covalent inhibitors and depleting native ligands to trap hidden conformational states, we obtained diverse X-ray structures of SETD8. These structures were used to seed distributed atomistic molecular dynamics simulations that generated a total of six milliseconds of trajectory data. Markov state models, built via an automated machine learning approach and corroborated experimentally, reveal how slow conformational motions and conformational states are relevant to catalysis. These findings provide molecular insight on enzymatic catalysis and allosteric mechanisms of a PKMT via its detailed conformational landscape.

PubMed: 31081496
DOI: 10.7554/eLife.45403

Experimental method

X-RAY DIFFRACTION (2 Å)