1i1n
From Proteopedia
(New page: 200px<br /> <applet load="1i1n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i1n, resolution 1.50Å" /> '''HUMAN PROTEIN L-ISO...) |
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| - | [[Image:1i1n.gif|left|200px]]<br /> | + | [[Image:1i1n.gif|left|200px]]<br /><applet load="1i1n" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1i1n" size=" | + | |
caption="1i1n, resolution 1.50Å" /> | caption="1i1n, resolution 1.50Å" /> | ||
'''HUMAN PROTEIN L-ISOASPARTATE O-METHYLTRANSFERASE WITH S-ADENOSYL HOMOCYSTEINE'''<br /> | '''HUMAN PROTEIN L-ISOASPARTATE O-METHYLTRANSFERASE WITH S-ADENOSYL HOMOCYSTEINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Spontaneous formation of isoaspartyl residues (isoAsp) disrupts the | + | 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== | ==About this Structure== | ||
| - | 1I1N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SAH as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-L-isoaspartate(D-aspartate)_O-methyltransferase Protein-L-isoaspartate(D-aspartate) O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.77 2.1.1.77] Full crystallographic information is available from [http:// | + | 1I1N is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-L-isoaspartate(D-aspartate)_O-methyltransferase Protein-L-isoaspartate(D-aspartate) O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.77 2.1.1.77] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I1N OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Carson, M.]] | [[Category: Carson, M.]] | ||
[[Category: Chattopadhyay, D.]] | [[Category: Chattopadhyay, D.]] | ||
| - | [[Category: Friedman, A | + | [[Category: Friedman, A M.]] |
| - | [[Category: Skinner, M | + | [[Category: Skinner, M M.]] |
| - | [[Category: Smith, C | + | [[Category: Smith, C D.]] |
[[Category: SAH]] | [[Category: SAH]] | ||
[[Category: methyltransferase]] | [[Category: methyltransferase]] | ||
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[[Category: s-adenosyl homocysteine]] | [[Category: s-adenosyl homocysteine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:07:02 2008'' |
Revision as of 11:07, 21 February 2008
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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 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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