PDBsum entry 4lwp

Transferase

PDB id: 4lwp

Contents

Protein chains

342 a.a.

Ligands

SAH ×2

PGE

Metals

IOD ×9

Waters ×57

References listed in PDB file

Key reference

• Title: Crystal structure of arginine methyltransferase 6 from trypanosoma brucei.
• Authors: C.Wang, Y.Zhu, J.Chen, X.Li, J.Peng, J.Chen, Y.Zou, Z.Zhang, H.Jin, P.Yang, J.Wu, L.Niu, Q.Gong, M.Teng, Y.Shi.
• Ref.: Plos One, 2014, 9, e87267. [DOI no: 10.1371/journal.pone.0087267]
• PubMed id: 24498306

Abstract

Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6) is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH). The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.