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| | <StructureSection load='4bps' size='340' side='right'caption='[[4bps]], [[Resolution|resolution]] 1.08Å' scene=''> | | <StructureSection load='4bps' size='340' side='right'caption='[[4bps]], [[Resolution|resolution]] 1.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bps]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/'streptomyces_hygroscopicus_subsp._ascomyceticus' 'streptomyces hygroscopicus subsp. ascomyceticus']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BPS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bps]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_hygroscopicus_subsp._ascomyceticus Streptomyces hygroscopicus subsp. ascomyceticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BPS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3EB:3-(2-CARBOXYETHYL)BENZOIC+ACID'>3EB</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]] 1.081Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3EB:3-(2-CARBOXYETHYL)BENZOIC+ACID'>3EB</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bps OCA], [https://pdbe.org/4bps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bps RCSB], [https://www.ebi.ac.uk/pdbsum/4bps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bps 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=4bps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bps OCA], [https://pdbe.org/4bps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bps RCSB], [https://www.ebi.ac.uk/pdbsum/4bps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bps ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FKBO_STRHY FKBO_STRHY] Involved in the biosynthesis of the macrocyclic amino acid-linked polyketides FK506 and FK520 which are potent immunosuppressants that prevent T-cell proliferation through initial binding to the immunophilin FKBP12. Catalyzes the hydrolysis of chorismate via a 1,4-conjugate elimination of water to yield (4R,5R)-4,5-dihydroxycyclohexa-1,5-dienecarboxylic acid (DCDC).<ref>PMID:21383123</ref> <ref>PMID:24036425</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: Streptomyces hygroscopicus subsp. ascomyceticus]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andexer, J N]] | + | [[Category: Streptomyces hygroscopicus subsp. ascomyceticus]] |
| - | [[Category: Diederichs, K]] | + | [[Category: Andexer JN]] |
| - | [[Category: Hubrich, F]] | + | [[Category: Diederichs K]] |
| - | [[Category: Juneja, P]] | + | [[Category: Hubrich F]] |
| - | [[Category: Welte, W]] | + | [[Category: Juneja P]] |
| - | [[Category: Hydrolase]]
| + | [[Category: Welte W]] |
| - | [[Category: Yjgf fold]]
| + | |
| Structural highlights
Function
FKBO_STRHY Involved in the biosynthesis of the macrocyclic amino acid-linked polyketides FK506 and FK520 which are potent immunosuppressants that prevent T-cell proliferation through initial binding to the immunophilin FKBP12. Catalyzes the hydrolysis of chorismate via a 1,4-conjugate elimination of water to yield (4R,5R)-4,5-dihydroxycyclohexa-1,5-dienecarboxylic acid (DCDC).[1] [2]
Publication Abstract from PubMed
Chorismate-converting enzymes are involved in many biosynthetic pathways leading to natural products and can often be used as tools for the synthesis of chemical building blocks. Chorismatases such as FkbO from Streptomyces species catalyse the hydrolysis of chorismate yielding (dihydro)benzoic acid derivatives. In contrast to many other chorismate-converting enzymes, the structure and catalytic mechanism of a chorismatase had not been previously elucidated. Here we present the crystal structure of the chorismatase FkbO in complex with a competitive inhibitor at 1.08A resolution. FkbO is a monomer in solution and exhibits pseudo-3-fold symmetry; the structure of the individual domains indicates a possible connection to the trimeric RidA/YjgF family and related enzymes. The co-crystallised inhibitor led to the identification of FkbO's active site in the cleft between the central and the C-terminal domains. A mechanism for FkbO is proposed based on both interactions between the inhibitor and the surrounding amino acids and an FkbO structure with chorismate modelled in the active site. We suggest that the methylene group of the chorismate enol ether takes up a proton from an active-site glutamic acid residue, thereby initiating chorismate hydrolysis. A similar chemistry has been described for isochorismatases, albeit implemented in an entirely different protein scaffold. This reaction model is supported by kinetic data from active-site variants of FkbO derived by site-directed mutagenesis.
Mechanistic Implications for the Chorismatase FkbO Based on the Crystal Structure.,Juneja P, Hubrich F, Diederichs K, Welte W, Andexer JN J Mol Biol. 2013 Sep 13. pii: S0022-2836(13)00575-5. doi:, 10.1016/j.jmb.2013.09.006. PMID:24036425[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Andexer JN, Kendrew SG, Nur-e-Alam M, Lazos O, Foster TA, Zimmermann AS, Warneck TD, Suthar D, Coates NJ, Koehn FE, Skotnicki JS, Carter GT, Gregory MA, Martin CJ, Moss SJ, Leadlay PF, Wilkinson B. Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin involves a previously undescribed family of enzymes acting on chorismate. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4776-81. PMID:21383123 doi:10.1073/pnas.1015773108
- ↑ Juneja P, Hubrich F, Diederichs K, Welte W, Andexer JN. Mechanistic Implications for the Chorismatase FkbO Based on the Crystal Structure. J Mol Biol. 2013 Sep 13. pii: S0022-2836(13)00575-5. doi:, 10.1016/j.jmb.2013.09.006. PMID:24036425 doi:10.1016/j.jmb.2013.09.006
- ↑ Juneja P, Hubrich F, Diederichs K, Welte W, Andexer JN. Mechanistic Implications for the Chorismatase FkbO Based on the Crystal Structure. J Mol Biol. 2013 Sep 13. pii: S0022-2836(13)00575-5. doi:, 10.1016/j.jmb.2013.09.006. PMID:24036425 doi:10.1016/j.jmb.2013.09.006
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