1I1N

HUMAN PROTEIN L-ISOASPARTATE O-METHYLTRANSFERASE WITH S-ADENOSYL HOMOCYSTEINE

Summary for 1I1N

• Entry DOI: 10.2210/pdb1i1n/pdb
• Related: 1DL5
• Descriptor: PROTEIN-L-ISOASPARTATE O-METHYLTRANSFERASE, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: methyltransferase, s-adenosyl homocysteine, protein repair, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P22061
• Total number of polymer chains: 1
• Total formula weight: 24921.62

Authors

Smith, C.D.,Chattopadhyay, D.,Carson, M.,Friedman, A.M.,Skinner, M.M. (deposition date: 2001-02-02, release date: 2002-03-13, Last modification date: 2023-08-09)

Primary citation

Smith, C.D.,Carson, M.,Friedman, A.M.,Skinner, M.M.,Delucas, L.,Chantalat, L.,Weise, L.,Shirasawa, T.,Chattopadhyay, D.
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.
Protein Sci., 11:625-635, 2002

PubMed Abstract: 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.

PubMed: 11847284
DOI: 10.1110/ps.37802

Experimental method

X-RAY DIFFRACTION (1.5 Å)