7dbl: Difference between revisions
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<StructureSection load='7dbl' size='340' side='right'caption='[[7dbl]], [[Resolution|resolution]] 1.84Å' scene=''> | <StructureSection load='7dbl' size='340' side='right'caption='[[7dbl]], [[Resolution|resolution]] 1.84Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7dbl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7dbl]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Penicillium_brevicompactum Penicillium brevicompactum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DBL FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MOA:MYCOPHENOLIC+ACID'>MOA</scene></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=7dbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dbl OCA], [https://pdbe.org/7dbl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dbl RCSB], [https://www.ebi.ac.uk/pdbsum/7dbl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dbl ProSAT]</span></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=7dbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dbl OCA], [https://pdbe.org/7dbl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dbl RCSB], [https://www.ebi.ac.uk/pdbsum/7dbl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dbl ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/MPAH2_PENBR MPAH2_PENBR] Type I acyl-CoA thioesterase; part of the gene cluster that mediates the biosynthesis of mycophenolic acid (MPA), the first isolated antibiotic natural product in the world obtained from a culture of Penicillium brevicompactum in 1893 (PubMed:31209052, PubMed:33843134). MpaH' acts as a peroxisomal acyl-CoA hydrolase that converts MPA-CoA into the final product MPA (PubMed:31209052, PubMed:33843134). The first step of the pathway is the synthesis of 5-methylorsellinic acid (5MOA) by the cytosolic polyketide synthase mpaC. 5MOA is then converted to the phthalide compound 5,7-dihydroxy-4,6-dimethylphthalide (DHMP) by the endoplasmic reticulum-bound cytochrome P450 monooxygenase mpaDE. MpaDE first catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). MpaDE then acts as a lactone synthase that catalyzes the ring closure to convert DHMB into DHMP. The next step is the prenylation of DHMP by the Golgi apparatus-associated prenyltransferase mpaA to yield farnesyl-DHMP (FDHMP). The ER-bound oxygenase mpaB then mediates the oxidative cleavage the C19-C20 double bond in FDHMP to yield FDHMP-3C via a mycophenolic aldehyde intermediate. The O-methyltransferase mpaG catalyzes the methylation of FDHMP-3C to yield MFDHMP-3C. After the cytosolic methylation of FDHMP-3C, MFDHMP-3C enters into peroxisomes probably via free diffusion due to its low molecular weight. Upon a peroxisomal CoA ligation reaction, catalyzed by a beta-oxidation component enzyme acyl-CoA ligase ACL891, MFDHMP-3C-CoA would then be restricted to peroxisomes for the following beta-oxidation pathway steps. The peroxisomal beta-oxidation machinery than converts MFDHMP-3C-CoA into MPA_CoA, via a beta-oxidation chain-shortening process. Finally mpaH acts as a peroxisomal acyl-CoA hydrolase with high substrate specificity toward MPA-CoA to release the final product MPA (PubMed:31209052) (Probable).<ref>PMID:31209052</ref> <ref>PMID:33843134</ref> <ref>PMID:31209052</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Penicillium brevicompactum]] | ||
[[Category: | [[Category: Li SY]] | ||
[[Category: | [[Category: You C]] | ||
