5v7p

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==Atomic structure of the eukaryotic intramembrane Ras methyltransferase ICMT (isoprenylcysteine carboxyl methyltransferase), in complex with a monobody==
==Atomic structure of the eukaryotic intramembrane Ras methyltransferase ICMT (isoprenylcysteine carboxyl methyltransferase), in complex with a monobody==
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<StructureSection load='5v7p' size='340' side='right' caption='[[5v7p]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='5v7p' size='340' side='right'caption='[[5v7p]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5v7p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Red_flour_beetle Red flour beetle] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V7P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V7P FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5v7p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tribolium_castaneum Tribolium castaneum] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V7P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V7P FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=MPG:[(Z)-OCTADEC-9-ENYL]+(2R)-2,3-BIS(OXIDANYL)PROPANOATE'>MPG</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UND:UNDECANE'>UND</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TcasGA2_TC013078 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7070 Red flour beetle])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=MPG:[(Z)-OCTADEC-9-ENYL]+(2R)-2,3-BIS(OXIDANYL)PROPANOATE'>MPG</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UND:UNDECANE'>UND</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-S-isoprenylcysteine_O-methyltransferase Protein-S-isoprenylcysteine O-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.100 2.1.1.100] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5v7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v7p OCA], [https://pdbe.org/5v7p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v7p RCSB], [https://www.ebi.ac.uk/pdbsum/5v7p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v7p ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5v7p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v7p OCA], [http://pdbe.org/5v7p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v7p RCSB], [http://www.ebi.ac.uk/pdbsum/5v7p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v7p ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/ICMT_TRICA ICMT_TRICA] Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.<ref>PMID:29342140</ref>
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The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of the AAX residues and methylation of the exposed prenylcysteine residue at its terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that resides in the endoplasmic reticulum. ICMT is the only cellular enzyme that is known to methylate prenylcysteine substrates; methylation is important for the biological functions of these substrates, such as the membrane localization and subsequent activity of RAS, prelamin A and RAB. Inhibition of ICMT has potential for combating progeria and cancer. Here we present an X-ray structure of ICMT, in complex with its cofactor, an ordered lipid molecule and a monobody inhibitor, at 2.3 A resolution. The active site spans cytosolic and membrane-exposed regions, indicating distinct entry routes for the cytosolic methyl donor, S-adenosyl-l-methionine, and for prenylcysteine substrates, which are associated with the endoplasmic reticulum membrane. The structure suggests how ICMT overcomes the topographical challenge and unfavourable energetics of bringing two reactants that have different cellular localizations together in a membrane environment-a relatively uncharacterized but defining feature of many integral membrane enzymes.
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Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT.,Diver MM, Pedi L, Koide A, Koide S, Long SB Nature. 2018 Jan 25;553(7689):526-529. doi: 10.1038/nature25439. Epub 2018 Jan, 17. PMID:29342140<ref>PMID:29342140</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5v7p" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Protein-S-isoprenylcysteine O-methyltransferase]]
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[[Category: Large Structures]]
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[[Category: Red flour beetle]]
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[[Category: Synthetic construct]]
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[[Category: Synthetic construct sequences]]
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[[Category: Tribolium castaneum]]
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[[Category: Diver, M M]]
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[[Category: Diver MM]]
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[[Category: Koide, A]]
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[[Category: Koide A]]
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[[Category: Koide, S]]
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[[Category: Koide S]]
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[[Category: Long, S B]]
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[[Category: Long SB]]
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[[Category: Pedi, L]]
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[[Category: Pedi L]]
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[[Category: Lcp]]
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[[Category: Membrane enzyme]]
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[[Category: Membrane protein]]
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[[Category: Methyltransferase]]
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[[Category: Transferase]]
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Current revision

Atomic structure of the eukaryotic intramembrane Ras methyltransferase ICMT (isoprenylcysteine carboxyl methyltransferase), in complex with a monobody

PDB ID 5v7p

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