1EAM

VACCINIA METHYLTRANSFERASE VP39 MUTANT (EC: 2.7.7.19)

Summary for 1EAM

• Entry DOI: 10.2210/pdb1eam/pdb
• Descriptor: PROTEIN (VP39), S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: methylated guanosine, methyltransferase mutant e233a, poly (a) polymerase, vaccinia, mrna processing, transcription, transferase
• Biological source: Vaccinia virus
• Total number of polymer chains: 1
• Total formula weight: 36247.81

Authors

Hu, G.,Hodel, A.E.,Gershon, P.D.,Quiocho, F.A. (deposition date: 1999-01-26, release date: 1999-06-14, Last modification date: 2023-12-27)

Primary citation

Hu, G.,Gershon, P.D.,Hodel, A.E.,Quiocho, F.A.
mRNA cap recognition: dominant role of enhanced stacking interactions between methylated bases and protein aromatic side chains.
Proc.Natl.Acad.Sci.USA, 96:7149-7154, 1999

PubMed Abstract: We have determined, by high resolution x-ray analysis, 10 structures comprising the mRNA cap-specific methyltransferase VP39 or specific mutants thereof in the presence of methylated nucleobase analogs (N1-methyladenine, N3-methyladenine, N1-methylcytosine, N3-methylcytosine) and their unmethylated counterparts, or nucleoside N7-methylguanosine. Together with solution affinity studies and previous crystallographic data for N7-methylguanosine and its phosphorylated derivatives, these data demonstrate that only methylated, positively charged bases are bound, indicating that their enhanced stacking with two aromatic side chains of VP39 (Tyr 22 and Phe 180) plays a dominant role in cap recognition. Four key features characterize this stacking interaction: (i) near perfect parallel alignment between the sandwiched methylated bases and aromatic side chains, (ii) substantial areas of overlap in the two-stacked rings, (iii) a 3.4-A interplanar spacing within the overlapping region, and (iv) positive charge in the heterocyclic nucleobase.

PubMed: 10377383
DOI: 10.1073/pnas.96.13.7149

Experimental method

X-RAY DIFFRACTION (2 Å)