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PDBsum entry 4myo
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PDB id:
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Transferase
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Title:
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Crystal structure of streptogramin group a antibiotic acetyltransferase vata from staphylococcus aureus
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Structure:
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Virginiamycin a acetyltransferase. Chain: a, b, c. Engineered: yes
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Source:
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Staphylococcus aureus. Organism_taxid: 1280. Strain: bm3093. Gene: vat. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.70Å
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R-factor:
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0.193
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R-free:
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0.254
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Authors:
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P.J.Stogios,G.Minasov,A.Dong,E.Evdokimova,V.Yim,M.Krishnamoorthy,R.Di Leo,P.Courvalin,A.Savchenko,W.F.Anderson,Center For Structural Genomics Of Infectious Diseases (Csgid)
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Key ref:
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P.J.Stogios
et al.
(2014).
Potential for reduction of streptogramin A resistance revealed by structural analysis of acetyltransferase VatA.
Antimicrob Agents Chemother,
58,
7083-7092.
PubMed id:
DOI:
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Date:
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27-Sep-13
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Release date:
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16-Oct-13
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Supersedes:
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PROCHECK
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Headers
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References
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P26839
(VATA_STAAU) -
Virginiamycin A acetyltransferase from Staphylococcus aureus
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Seq:
Struc:
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219 a.a.
211 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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DOI no:
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Antimicrob Agents Chemother
58:7083-7092
(2014)
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PubMed id:
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Potential for reduction of streptogramin A resistance revealed by structural analysis of acetyltransferase VatA.
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P.J.Stogios,
M.L.Kuhn,
E.Evdokimova,
P.Courvalin,
W.F.Anderson,
A.Savchenko.
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ABSTRACT
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Combinations of group A and B streptogramins (i.e., dalfopristin and
quinupristin) are "last-resort" antibiotics for the treatment of
infections caused by Gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Resistance
to streptogramins has arisen via multiple mechanisms, including the deactivation
of the group A component by the large family of virginiamycin
O-acetyltransferase (Vat) enzymes. Despite the structural elucidation performed
for the VatD acetyltransferase, which provided a general molecular framework for
activity, a detailed characterization of the essential catalytic and antibiotic
substrate-binding determinants in Vat enzymes is still lacking. We have
determined the crystal structure of S. aureus VatA in apo, virginiamycin M1- and
acetyl-coenzyme A (CoA)-bound forms and provide an extensive mutagenesis and
functional analysis of the structural determinants required for catalysis and
streptogramin A recognition. Based on an updated genomic survey across the Vat
enzyme family, we identified key conserved residues critical for VatA activity
that are not part of the O-acetylation catalytic apparatus. Exploiting such
constraints of the Vat active site may lead to the development of streptogramin
A compounds that evade inactivation by Vat enzymes while retaining binding to
their ribosomal target.
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Links
