8eh0: Difference between revisions
New page: '''Unreleased structure''' The entry 8eh0 is ON HOLD Authors: Porter, N.J., Almhjell, P.J., Arnold, F.H. Description: Engineered tyrosine synthase (TmTyrS1) derived from T. maritima Tr... |
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The | ==Engineered tyrosine synthase (TmTyrS1) derived from T. maritima TrpB with Ser bound as the amino-acrylate intermediate and complexed with quinoline N-oxide== | ||
<StructureSection load='8eh0' size='340' side='right'caption='[[8eh0]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8eh0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8EH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EH0 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JO:2-{[(E)-{3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYLIDENE]AMINO}PROP-2-ENOIC+ACID'>0JO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QOX:1-oxo-1lambda~5~-quinoline'>QOX</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=8eh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8eh0 OCA], [https://pdbe.org/8eh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8eh0 RCSB], [https://www.ebi.ac.uk/pdbsum/8eh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8eh0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRPB1_THEMA TRPB1_THEMA] The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we introduce a new enzymatic transformation for L-tyrosine synthesis by demonstrating that the beta-subunit of tryptophan synthase-which natively couples indole and L-serine to form L-tryptophan-can act as a latent 'tyrosine synthase'. A single substitution of a near-universally conserved catalytic residue unlocks activity toward simple phenol analogs and yields exclusive para carbon-carbon bond formation to furnish L-tyrosines. Structural and mechanistic studies show how a new active-site water molecule orients phenols for a nonnative mechanism of alkylation, with additional directed evolution resulting in a net >30,000-fold rate enhancement. This new biocatalyst can be used to efficiently prepare valuable L-tyrosine analogs at gram scales and provides the missing chemistry for a conceptually different pathway to L-tyrosine. | |||
The beta-subunit of tryptophan synthase is a latent tyrosine synthase.,Almhjell PJ, Johnston KE, Porter NJ, Kennemur JL, Bhethanabotla VC, Ducharme J, Arnold FH Nat Chem Biol. 2024 May 14. doi: 10.1038/s41589-024-01619-z. PMID:38744987<ref>PMID:38744987</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Almhjell | <div class="pdbe-citations 8eh0" style="background-color:#fffaf0;"></div> | ||
[[Category: Arnold | |||
[[Category: Porter | ==See Also== | ||
*[[Tryptophan synthase 3D structures|Tryptophan synthase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermotoga maritima]] | |||
[[Category: Almhjell PJ]] | |||
[[Category: Arnold FH]] | |||
[[Category: Porter NJ]] | |||
Latest revision as of 10:35, 3 July 2024
Engineered tyrosine synthase (TmTyrS1) derived from T. maritima TrpB with Ser bound as the amino-acrylate intermediate and complexed with quinoline N-oxideEngineered tyrosine synthase (TmTyrS1) derived from T. maritima TrpB with Ser bound as the amino-acrylate intermediate and complexed with quinoline N-oxide
Structural highlights
FunctionTRPB1_THEMA The beta subunit is responsible for the synthesis of L-tryptophan from indole and L-serine. Publication Abstract from PubMedAromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we introduce a new enzymatic transformation for L-tyrosine synthesis by demonstrating that the beta-subunit of tryptophan synthase-which natively couples indole and L-serine to form L-tryptophan-can act as a latent 'tyrosine synthase'. A single substitution of a near-universally conserved catalytic residue unlocks activity toward simple phenol analogs and yields exclusive para carbon-carbon bond formation to furnish L-tyrosines. Structural and mechanistic studies show how a new active-site water molecule orients phenols for a nonnative mechanism of alkylation, with additional directed evolution resulting in a net >30,000-fold rate enhancement. This new biocatalyst can be used to efficiently prepare valuable L-tyrosine analogs at gram scales and provides the missing chemistry for a conceptually different pathway to L-tyrosine. The beta-subunit of tryptophan synthase is a latent tyrosine synthase.,Almhjell PJ, Johnston KE, Porter NJ, Kennemur JL, Bhethanabotla VC, Ducharme J, Arnold FH Nat Chem Biol. 2024 May 14. doi: 10.1038/s41589-024-01619-z. PMID:38744987[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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