4M37

Crystal structure of Trypanosoma brucei protein arginine methyltransferase 7 complex with AdoHcy

Summary for 4M37

• Entry DOI: 10.2210/pdb4m37/pdb
• Related: 4M36 4M38
• Descriptor: Protein arginine N-methyltransferase 7, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: methyltransferase, transferase
• Biological source: Trypanosoma brucei brucei
• Cellular location: Cytoplasm: Q582G4
• Total number of polymer chains: 1
• Total formula weight: 39369.88

Authors

Wang, C.,Zhu, Y.,Shi, Y. (deposition date: 2013-08-06, release date: 2014-04-23, Last modification date: 2024-05-29)

Primary citation

Wang, C.,Zhu, Y.,Caceres, T.B.,Liu, L.,Peng, J.,Wang, J.,Chen, J.,Chen, X.,Zhang, Z.,Zuo, X.,Gong, Q.,Teng, M.,Hevel, J.M.,Wu, J.,Shi, Y.
Structural determinants for the strict monomethylation activity by trypanosoma brucei protein arginine methyltransferase 7.
Structure, 22:756-768, 2014

PubMed Abstract: Trypanosoma brucei protein arginine methyltransferase 7 (TbPRMT7) exclusively generates monomethylarginine (MMA), which directs biological consequences distinct from that of symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). However, determinants controlling the strict monomethylation activity are unknown. We present the crystal structure of the TbPRMT7 active core in complex with S-adenosyl-L-homocysteine (AdoHcy) and a histone H4 peptide substrate. In the active site, residues E172, E181, and Q329 hydrogen bond the guanidino group of the target arginine and align the terminal guanidino nitrogen in a position suitable for nucleophilic attack on the methyl group of S-adenosyl-L-methionine (AdoMet). Structural comparisons and isothermal titration calorimetry data suggest that the TbPRMT7 active site is narrower than those of protein arginine dimethyltransferases, making it unsuitable to bind MMA in a manner that would support a second turnover, thus abolishing the production of SDMA and ADMA. Our results present the structural interpretations for the monomethylation activity of TbPRMT7.

PubMed: 24726341
DOI: 10.1016/j.str.2014.03.003

Experimental method

X-RAY DIFFRACTION (1.7 Å)