1nv8
N5-glutamine methyltransferase, HemK
|
OverviewOverview
Posttranslational methylation of release factors on the glutamine residue, of a conserved GGQ motif is required for efficient termination of protein, synthesis. This methylation is performed by an N(5)-glutamine, methyltransferase called PrmC/HemK, whose crystal structure we report here, at 2.2 A resolution. The electron density at the active site appears to, contain a mixture of the substrates, S-adenosyl-L-methionine (AdoMet) and, glutamine, and the products, S-adenosyl-L-homocysteine (AdoHcy) and, N(5)-methylglutamine. The C-terminal domain of PrmC adopts the canonical, AdoMet-dependent methyltransferase fold and shares structural similarity, with the nucleotide N-methyltransferases in the active site, including use, of a conserved (D/N)PPY motif to select and position the glutamine, substrate. Residues of the PrmC (197)NPPY(200) motif form hydrogen bonds, that position the planar Gln side chain such that the lone-pair electrons, on the nitrogen nucleophile are oriented toward the methyl group of, AdoMet. In the product complex, the methyl group remains pointing toward, the sulfur, consistent with either an sp(3)-hybridized, positively charged, Gln nitrogen, or a neutral sp(2)-hybridized nitrogen in a strained, conformation. Due to steric overlap within the active site, proton loss, and formation of the neutral planar methylamide product are likely to, occur during or after product release. These structures, therefore, represent intermediates along the catalytic pathway of PrmC and show how, the (D/N)PPY motif can be used to select a wide variety substrates.
About this StructureAbout this Structure
1NV8 is a Single protein structure of sequence from Thermotoga maritima with SAM and MEQ as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structures along the catalytic pathway of PrmC/HemK, an N5-glutamine AdoMet-dependent methyltransferase., Schubert HL, Phillips JD, Hill CP, Biochemistry. 2003 May 20;42(19):5592-9. PMID:12741815
Page seeded by OCA on Sat Nov 24 23:51:42 2007