1dl5
From Proteopedia
(New page: 200px<br /><applet load="1dl5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dl5, resolution 1.8Å" /> '''PROTEIN-L-ISOASPARTAT...) |
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| - | [[Image:1dl5.gif|left|200px]]<br /><applet load="1dl5" size=" | + | [[Image:1dl5.gif|left|200px]]<br /><applet load="1dl5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dl5, resolution 1.8Å" /> | caption="1dl5, resolution 1.8Å" /> | ||
'''PROTEIN-L-ISOASPARTATE O-METHYLTRANSFERASE'''<br /> | '''PROTEIN-L-ISOASPARTATE O-METHYLTRANSFERASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Formation of isoaspartyl residues is one of several processes | + | BACKGROUND: Formation of isoaspartyl residues is one of several processes that damage proteins as they age. Protein L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) is a conserved and nearly ubiquitous enzyme that catalyzes the repair of proteins damaged by isoaspartyl formation. RESULTS: We have determined the first structure of a PIMT from crystals of the T. maritima enzyme complexed to S-adenosyl-L-homocysteine (AdoHcy) and refined it to 1.8 A resolution. Although PIMT forms one structural unit, the protein can be divided functionally into three subdomains. The central subdomain closely resembles other S-adenosyl-L-methionine-dependent methyltransferases but bears a striking alteration of topological connectivity, which is not shared by any other member of this family. Rather than arranged as a mixed beta sheet with topology 6 upward arrow7 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow, the central sheet of PIMT is reorganized to 7 upward arrow6 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow. AdoHcy is largely buried between the N-terminal and central subdomains by a conserved and largely hydrophobic loop on one rim of the binding cleft, and a conserved Ser/Thr-rich beta strand on the other. The Ser/Thr-rich strand may provide hydrogen bonds for specific interactions with isoaspartyl substrates. The side chain of Ile-206, a conserved residue, crosses the cleft, restricting access to the donor methyl group to a deep well, the putative isoaspartyl methyl acceptor site. CONCLUSIONS: The structure of PIMT reveals a unique modification of the methyltransferase fold along with a site for specific recognition of isoaspartyl substrates. The sequence conservation among PIMTs suggests that the current structure should prove a reliable model for understanding the repair of isoaspartyl damage in all organisms. |
==About this Structure== | ==About this Structure== | ||
| - | 1DL5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with CD, CL and SAH as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1DL5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with <scene name='pdbligand=CD:'>CD</scene>, <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=SAH:'>SAH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1DL5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thermotoga maritima]] | [[Category: Thermotoga maritima]] | ||
| - | [[Category: Friedman, A | + | [[Category: Friedman, A M.]] |
| - | [[Category: Puvathingal, J | + | [[Category: Puvathingal, J M.]] |
| - | [[Category: Skinner, M | + | [[Category: Skinner, M M.]] |
| - | [[Category: Walter, R | + | [[Category: Walter, R L.]] |
[[Category: CD]] | [[Category: CD]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: protein repair]] | [[Category: protein repair]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:17:46 2008'' |
Revision as of 10:17, 21 February 2008
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PROTEIN-L-ISOASPARTATE O-METHYLTRANSFERASE
Overview
BACKGROUND: Formation of isoaspartyl residues is one of several processes that damage proteins as they age. Protein L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) is a conserved and nearly ubiquitous enzyme that catalyzes the repair of proteins damaged by isoaspartyl formation. RESULTS: We have determined the first structure of a PIMT from crystals of the T. maritima enzyme complexed to S-adenosyl-L-homocysteine (AdoHcy) and refined it to 1.8 A resolution. Although PIMT forms one structural unit, the protein can be divided functionally into three subdomains. The central subdomain closely resembles other S-adenosyl-L-methionine-dependent methyltransferases but bears a striking alteration of topological connectivity, which is not shared by any other member of this family. Rather than arranged as a mixed beta sheet with topology 6 upward arrow7 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow, the central sheet of PIMT is reorganized to 7 upward arrow6 downward arrow5 upward arrow4 upward arrow1 upward arrow2 upward arrow3 upward arrow. AdoHcy is largely buried between the N-terminal and central subdomains by a conserved and largely hydrophobic loop on one rim of the binding cleft, and a conserved Ser/Thr-rich beta strand on the other. The Ser/Thr-rich strand may provide hydrogen bonds for specific interactions with isoaspartyl substrates. The side chain of Ile-206, a conserved residue, crosses the cleft, restricting access to the donor methyl group to a deep well, the putative isoaspartyl methyl acceptor site. CONCLUSIONS: The structure of PIMT reveals a unique modification of the methyltransferase fold along with a site for specific recognition of isoaspartyl substrates. The sequence conservation among PIMTs suggests that the current structure should prove a reliable model for understanding the repair of isoaspartyl damage in all organisms.
About this Structure
1DL5 is a Single protein structure of sequence from Thermotoga maritima with , and as ligands. 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 protein isoaspartyl methyltransferase: a catalyst for protein repair., Skinner MM, Puvathingal JM, Walter RL, Friedman AM, Structure. 2000 Nov 15;8(11):1189-201. PMID:11080641
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