1i1n
From Proteopedia
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HUMAN PROTEIN L-ISOASPARTATE O-METHYLTRANSFERASE WITH S-ADENOSYL HOMOCYSTEINE
Overview
Spontaneous formation of isoaspartyl residues (isoAsp) disrupts the, structure and function of many normal proteins. Protein isoaspartyl, methyltransferase (PIMT) reverts many isoAsp residues to aspartate as a, protein repair process. We have determined the crystal structure of human, protein isoaspartyl methyltransferase (HPIMT) complexed with adenosyl, homocysteine (AdoHcy) to 1.6-A resolution. The core structure has a, nucleotide binding domain motif, which is structurally homologous with the, N-terminal domain of the bacterial Thermotoga maritima PIMT. Highly, conserved residues in PIMTs among different phyla are placed at positions, critical to AdoHcy binding and orienting the isoAsp residue substrate for, methylation. The AdoHcy is completely enclosed within the HPIMT and a, conformational change must occur to allow exchange with adenosyl, methionine (AdoMet). An ordered sequential enzyme mechanism is supported, because C-terminal residues involved with AdoHcy binding also form the, isoAsp peptide binding site, and a change of conformation to allow AdoHcy, to escape would preclude peptide binding. Modeling experiments indicated, isoAsp groups observed in some known protein crystal structures could bind, to the HPIMT active site.
About this Structure
1I1N is a Single protein structure of sequence from Homo sapiens with SAH as ligand. Active as Protein-L-isoaspartate(D-aspartate) O-methyltransferase, with EC number 2.1.1.77 Full crystallographic information is available from OCA.
Reference
Crystal structure of human L-isoaspartyl-O-methyl-transferase with S-adenosyl homocysteine at 1.6-A resolution and modeling of an isoaspartyl-containing peptide at the active site., Smith CD, Carson M, Friedman AM, Skinner MM, Delucas L, Chantalat L, Weise L, Shirasawa T, Chattopadhyay D, Protein Sci. 2002 Mar;11(3):625-35. PMID:11847284
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