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PDBsum entry 1css
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Oxo-acid-lyase
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PDB id
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1css
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References listed in PDB file
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Key reference
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Title
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Alpha-Fluoro acid and alpha-Fluoro amide analogs of acetyl-Coa as inhibitors of citrate synthase: effect of pka matching on binding affinity and hydrogen bond length.
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Authors
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B.Schwartz,
D.G.Drueckhammer,
K.C.Usher,
S.J.Remington.
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Ref.
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Biochemistry, 1995,
34,
15459-15466.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
97%.
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Abstract
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An alpha-fluoro acid analog and an alpha-fluoro amide analog of acetyl-CoA have
been synthesized. The ternary complexes of these inhibitors with oxaloacetate
and citrate synthase have been crystallized and their structures analyzed at 1.7
A resolution. The structures are similar to those reported for the corresponding
non-fluorinated analogs (Usher et al., 1994), with all forming unusually short
hydrogen bonds to Asp 375. The alpha-fluoro amide analog binds with an affinity
1.5-fold lower than that of a previously described amide analog lacking the
alpha-fluoro group. The alpha-fluoro acid analog binds with a 50-fold decreased
affinity relative to the corresponding unfluorinated analog. The binding
affinities are consistent with increased strengths of hydrogen bonds to Asp 375
with closer matching of pKa values between hydrogen bond donors and acceptors.
The results do not support any direct correlation between hydrogen bond strength
and hydrogen bond length in enzyme-inhibitor complexes.
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Secondary reference #1
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Title
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A very short hydrogen bond provides only moderate stabilization of an enzyme-Inhibitor complex of citrate synthase.
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Authors
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K.C.Usher,
S.J.Remington,
D.P.Martin,
D.G.Drueckhammer.
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Ref.
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Biochemistry, 1994,
33,
7753-7759.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Proposed mechanism for the condensation reaction of citrate synthase: 1.9-A structure of the ternary complex with oxaloacetate and carboxymethyl coenzyme a.
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Authors
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M.Karpusas,
B.Branchaud,
S.J.Remington.
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Ref.
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Biochemistry, 1990,
29,
2213-2219.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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Crystal structure analysis and molecular model of a complex of citrate synthase with oxaloacetate and s-Acetonyl-Coenzyme a.
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Authors
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G.Wiegand,
S.Remington,
J.Deisenhofer,
R.Huber.
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Ref.
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J Mol Biol, 1984,
174,
205-219.
[DOI no: ]
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PubMed id
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Figure 2.
FIG. 2. The small omains of the closed form (C2) and the closed form (P4,2,2) are optimally
superimposed and shown in the stereo diagram. The conformations also differ substantially for internal
residues as ndicated specifically for some residues.
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The above figure is
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #4
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Title
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Crystallographic refinement and atomic models of two different forms of citrate synthase at 2.7 and 1.7 a resolution.
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Authors
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S.Remington,
G.Wiegand,
R.Huber.
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Ref.
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J Mol Biol, 1982,
158,
111-152.
[DOI no: ]
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PubMed id
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Figure 1.
BVIE
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Figure 19.
FIG. 19. Stereo drawing of the citryl-thioether-CoA analogue ((XC%NPH6) difference Fourier map
superimposed on the monoclinic model. Contours are at +49 e. with negative contours dashed. The
Figure is discussd in the text.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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