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PDBsum entry 3dp0
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Contents |
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* Residue conservation analysis
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PDB id:
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Lyase
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Title:
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Crystal structure of (3r)-hydroxyacyl-acyl carrier protein dehydratase (fabz) from helicobacter pylori in complex with compound 3m
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Structure:
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(3r)-hydroxymyristoyl-acyl carrier protein dehydratase. Chain: a, b, c, d, e, f. Engineered: yes
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Source:
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Helicobacter pylori. Campylobacter pylori. Organism_taxid: 210. Strain: ss1. Gene: fabz. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.50Å
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R-factor:
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0.201
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R-free:
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0.237
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Authors:
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L.Zhang,L.He,X.Liu,H.Liu,X.Shen,H.Jiang
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Key ref:
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L.He
et al.
(2009).
Discovering potent inhibitors against the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Helicobacter pylori: structure-based design, synthesis, bioassay, and crystal structure determination.
J Med Chem,
52,
2465-2481.
PubMed id:
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Date:
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07-Jul-08
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Release date:
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05-May-09
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PROCHECK
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Headers
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References
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Q5G940
(Q5G940_HELPX) -
3-hydroxyacyl-[acyl-carrier-protein] dehydratase FabZ from Helicobacter pylori
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Seq:
Struc:
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159 a.a.
152 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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Enzyme class:
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E.C.4.2.1.59
- 3-hydroxyacyl-[acyl-carrier-protein] dehydratase.
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Reaction:
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a (3R)-hydroxyacyl-[ACP] = a (2E)-enoyl-[ACP] + H2O
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(3R)-3-hydroxyacyl-[acyl-carrier protein]
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=
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trans-2-enoyl-[acyl- carrier protein]
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+
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H(2)O
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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J Med Chem
52:2465-2481
(2009)
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PubMed id:
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Discovering potent inhibitors against the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Helicobacter pylori: structure-based design, synthesis, bioassay, and crystal structure determination.
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L.He,
L.Zhang,
X.Liu,
X.Li,
M.Zheng,
H.Li,
K.Yu,
K.Chen,
X.Shen,
H.Jiang,
H.Liu.
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ABSTRACT
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The discovery of HpFabZ inhibitors is now of special interest in the treatment
of various gastric diseases. In this work, three series of derivatives
(compounds 3, 4, and 5) were designed, synthesized, and their biological
activities were investigated as potential HpFabZ inhibitors in a two phased
manner. First, we designed and synthesized two series of derivatives (3a-r and
4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k,
3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2
muM. Second, a focused combinatorial library containing 280 molecules was
designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and
synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was
46 times higher than that of the hit 1. The high hit rate and the potency of the
new HpFabZ inhibitors demonstrated the efficiency of the strategy for the
focused library design and virtual screening.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.K.Agarwal,
and
C.W.Fishwick
(2010).
Structure-based design of anti-infectives.
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Ann N Y Acad Sci,
1213,
20-45.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
