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==Crystal structure of the Candida albicans Methionine Synthase in complex with Glutamine==
==Crystal structure of the Candida albicans Methionine Synthase in complex with Glutamine==
<StructureSection load='4l6o' size='340' side='right' caption='[[4l6o]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
<StructureSection load='4l6o' size='340' side='right'caption='[[4l6o]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4l6o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Canal Canal]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L6O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L6O FirstGlance]. <br>
<table><tr><td colspan='2'>[[4l6o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans_SC5314 Candida albicans SC5314]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L6O FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4l5z|4l5z]], [[4l61|4l61]], [[4l64|4l64]], [[4l65|4l65]], [[4l6h|4l6h]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLN:GLUTAMINE'>GLN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CaO19.10083, CaO19.2551, MET6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=237561 CANAL])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4l6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l6o OCA], [https://pdbe.org/4l6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l6o RCSB], [https://www.ebi.ac.uk/pdbsum/4l6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l6o ProSAT]</span></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5-methyltetrahydropteroyltriglutamate--homocysteine_S-methyltransferase 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.14 2.1.1.14] </span></td></tr>
<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=4l6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l6o OCA], [http://pdbe.org/4l6o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4l6o RCSB], [http://www.ebi.ac.uk/pdbsum/4l6o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4l6o ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/METE_CANAL METE_CANAL]] Catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine resulting in methionine formation.[HAMAP-Rule:MF_00172]  
[https://www.uniprot.org/uniprot/METE_CANAL METE_CANAL] Catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine resulting in methionine formation.[HAMAP-Rule:MF_00172]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cobalamin-independent methionine synthase from Candida albicans, known as Met6p, is a 90-kDa enzyme that consists of two (betaalpha)8 barrels. The active site is located between the two domains and has binding sites for a zinc ion and substrates l-homocysteine and 5-methyl-tetrahydrofolate-glutamate3. Met6p catalyzes transfer of the methyl group of 5-methyl-tetrahydrofolate-glutamate3 to the l-homocysteine thiolate to generate methionine. Met6p is essential for fungal growth, and we currently pursue it as an antifungal drug design target. Here we report the binding of l-homocysteine, methionine, and several folate analogs. We show that binding of l-homocysteine or methionine results in conformational rearrangements at the amino acid binding pocket, moving the catalytic zinc into position to activate the thiol group. We also map the folate binding pocket and identify specific binding residues, like Asn126, whose mutation eliminates catalytic activity. We also report the development of a robust fluorescence-based activity assay suitable for high-throughput screening. We use this assay and an X-ray structure to characterize methotrexate as a weak inhibitor of fungal Met6p.


Structural analysis of a fungal methionine synthase with substrates and inhibitors.,Ubhi D, Kago G, Monzingo AF, Robertus JD J Mol Biol. 2014 Apr 17;426(8):1839-47. doi: 10.1016/j.jmb.2014.02.006. Epub 2014, Feb 11. PMID:24524835<ref>PMID:24524835</ref>
==See Also==
 
*[[Methionine synthase 3D structures|Methionine synthase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4l6o" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: 5-methyltetrahydropteroyltriglutamate--homocysteine S-methyltransferase]]
[[Category: Candida albicans SC5314]]
[[Category: Canal]]
[[Category: Large Structures]]
[[Category: Robertus, J D]]
[[Category: Robertus JD]]
[[Category: Ubhi, D]]
[[Category: Ubhi D]]
[[Category: Cobalamin-independent]]
[[Category: Dual tim barrel]]
[[Category: Fungal]]
[[Category: Methionine synthase]]
[[Category: Surface entropy reduction]]
[[Category: Transferase]]

Latest revision as of 15:17, 1 March 2024

Crystal structure of the Candida albicans Methionine Synthase in complex with GlutamineCrystal structure of the Candida albicans Methionine Synthase in complex with Glutamine

Structural highlights

4l6o is a 1 chain structure with sequence from Candida albicans SC5314. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.88Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

METE_CANAL Catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine resulting in methionine formation.[HAMAP-Rule:MF_00172]

See Also

4l6o, resolution 1.88Å

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OCA
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