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PDBsum entry 5n8c
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PDB id:
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Hydrolase
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Title:
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Crystal structure of pseudomonas aeruginosa lpxc complexed with inhibitor
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Structure:
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Udp-3-o-acyl-n-acetylglucosamine deacetylase. Chain: a, b. Synonym: udp-3-o-acyl-glcnac deacetylase,udp-3-o-[r-3- hydroxymyristoyl]-n-acetylglucosamine deacetylase. Engineered: yes. Mutation: yes
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Source:
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Pseudomonas aeruginosa. Organism_taxid: 287. Gene: lpxc, enva, pa4406. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta 2.
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Resolution:
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1.90Å
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R-factor:
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0.152
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R-free:
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0.203
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Authors:
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J.B.Cross,M.D.Ryan,J.Zhang,R.K.Cheng,M.Wood,O.A.Andersen,M.Brooks, J.Kwong,J.Barker
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Key ref:
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J.Zhang
et al.
(2017).
Structure-based discovery of LpxC inhibitors.
Bioorg Med Chem Lett,
27,
1670-1680.
PubMed id:
DOI:
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Date:
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23-Feb-17
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Release date:
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29-Mar-17
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PROCHECK
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Headers
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References
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P47205
(LPXC_PSEAE) -
UDP-3-O-acyl-N-acetylglucosamine deacetylase from Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)
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Seq:
Struc:
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303 a.a.
300 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.3.5.1.108
- UDP-3-O-acyl-N-acetylglucosamine deacetylase.
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Reaction:
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a UDP-3-O-[(3R)-3-hydroxyacyl]-N-acetyl-alpha-D-glucosamine + H2O = a UDP-3-O-[(3R)-3-hydroxyacyl]-alpha-D-glucosamine + acetate
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UDP-3-O-[(3R)-3-hydroxyacyl]-N-acetyl-alpha-D-glucosamine
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+
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H2O
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=
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UDP-3-O-[(3R)-3-hydroxyacyl]-alpha-D-glucosamine
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+
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acetate
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Cofactor:
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Zn(2+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Bioorg Med Chem Lett
27:1670-1680
(2017)
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PubMed id:
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Structure-based discovery of LpxC inhibitors.
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J.Zhang,
A.Chan,
B.Lippa,
J.B.Cross,
C.Liu,
N.Yin,
J.A.Romero,
J.Lawrence,
R.Heney,
P.Herradura,
J.Goss,
C.Clark,
C.Abel,
Y.Zhang,
K.M.Poutsiaka,
F.Epie,
M.Conrad,
A.Mahamoon,
K.Nguyen,
A.Chavan,
E.Clark,
T.C.Li,
R.K.Cheng,
M.Wood,
O.A.Andersen,
M.Brooks,
J.Kwong,
J.Barker,
I.B.Parr,
Y.Gu,
M.D.Ryan,
S.Coleman,
C.A.Metcalf.
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ABSTRACT
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The emergence and spread of multidrug-resistant (MDR) Gram negative bacteria
presents a serious threat for public health. Novel antimicrobials that could
overcome the resistance problems are urgently needed.
UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a
cytosolic zinc-based deacetylase that catalyzes the first committed step in the
biosynthesis of lipid A, which is essential for the survival of Gram-negative
bacteria. Our efforts toward the discovery of novel LpxC inhibitors are
presented herein.
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Links
