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PDBsum entry 5e7q
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PDB id:
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Transferase
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Title:
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Acyl-coa synthetase ptma2 from streptomyces platensis
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Structure:
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Acyl-coa synthetase. Chain: a, b. Synonym: ptma2. Engineered: yes. Mutation: yes
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Source:
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Streptomyces platensis subsp. Rosaceus. Organism_taxid: 684832. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.23Å
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R-factor:
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0.175
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R-free:
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0.206
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Authors:
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J.Osipiuk,M.E.Cuff,C.Hatzos-Skintges,M.Endres,G.Babnigg,J.Rudolf, M.Ma,C.Y.Chang,B.Shen,G.N.Phillips Jr.,A.Joachimiak,Midwest Center For Structural Genomics (Mcsg),Enzyme Discovery For Natural Product Biosynthesis (Natpro)
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Key ref:
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N.Wang
et al.
(2018).
Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.
Nat Chem Biol,
14,
730-737.
PubMed id:
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Date:
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12-Oct-15
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Release date:
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21-Oct-15
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PROCHECK
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Headers
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References
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A0A0A0V031
(A0A0A0V031_STRPT) -
PtmA2 from Streptomyces platensis
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Seq:
Struc:
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522 a.a.
509 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Nat Chem Biol
14:730-737
(2018)
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PubMed id:
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Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.
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N.Wang,
J.D.Rudolf,
L.B.Dong,
J.Osipiuk,
C.Hatzos-Skintges,
M.Endres,
C.Y.Chang,
G.Babnigg,
A.Joachimiak,
G.N.Phillips,
B.Shen.
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ABSTRACT
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Acyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a
two-step reaction of adenylation followed by thioesterification. Here, we report
the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional
separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA
ligases from the biosynthetic pathway of platensimycin and platencin, are
necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and
ptmA2 resulted in the accumulation of free acid and adenylate intermediates,
respectively. Enzymatic and structural characterization of PtmA2 confirmed its
ability to only catalyze thioesterification. Structural characterization of
PtmA2 revealed it binds both free acid and adenylate substrates and undergoes
the established mechanism of domain alternation. Finally, site-directed
mutagenesis restored both the adenylation and complete CoA activation reactions.
This study challenges the currently accepted paradigm of adenylating enzymes and
inspires future investigations on functionally separated acyl-CoA ligases and
their ramifications in biology.
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Links
