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PDBsum entry 1hnh
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Refined structures of beta-Ketoacyl-Acyl carrier protein synthase III.
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Authors
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X.Qiu,
C.A.Janson,
W.W.Smith,
M.Head,
J.Lonsdale,
A.K.Konstantinidis.
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Ref.
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J Mol Biol, 2001,
307,
341-356.
[DOI no: ]
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PubMed id
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Abstract
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beta-Ketoacyl-acyl carrier protein synthase III (FabH) is a condensing enzyme
that plays central roles in fatty acid biosynthesis. Three-dimensional
structures of E. coli FabH in the presence and absence of ligands have been
refined to 1.46 A resolution. The structures of improved accuracy revealed
detailed interactions involved in ligand binding. These structures also provided
new insights into the FabH mechanism, e.g. the possible role of a water or
hydroxyl anion in Cys112 deprotonation. A structure of the apo enzyme uncovered
large conformational changes in the active site, exemplified by the disordering
of four essential loops (84-86, 146-152, 185-217 and 305-307) and the movement
of catalytic residues (Cys112 and His244). The disordering of the loops leads to
greater than 50 % reduction in the FabH dimer interface, suggesting a dynamic
nature for an unusually large portion of the dimer interface. The existence of a
large solvent-accessible channel in the dimer interface as well as two
cis-peptides (cis-Pro88 and cis-Phe308) in two of the disordered loops may
explain the observed structural instabilities.
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Figure 3.
Figure 3. Electron density for Cys112 and a bound phosphate
ion in the O-FabH Structure. (a) The SA-omit map at Cys112,
contoured at 1.5 s. The extra density, centered at 2.3 Å
from the Sg atom, could be a tightly bound water molecule or
hydroxyl anion (OH -). (b) The density for a bound phosphate
ion, also contoured at 1.5 s. Broken lines indicate the hydrogen
bonds (distances labeled) between the phosphate ion and FabH.
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Figure 4.
Figure 4. The CoA binding mode observed in the FabH+CoA
structure. (a) The electron density for the bound CoA molecule
contoured at 1.0 s. Atoms are colored in the same way as in
previous figures. (b) Stereoview of the CoA molecule in the FabH
active site tunnel. Amino acid residues are labeled and hydrogen
bonds are shown with broken lines. CoA is drawn in thicker lines
with the carbon atoms in purple. (c) Stereoview of Arg42 and its
role in stabilizing helices La5 and La2. Hydrogen bonding
interactions are shown in red dashed lines. The adenine of CoA
is shown with magenta bonds.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
307,
341-356)
copyright 2001.
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Secondary reference #1
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Title
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Crystal structure of beta-Ketoacyl-Acyl carrier protein synthase III. A key condensing enzyme in bacterial fatty acid biosynthesis.
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Authors
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X.Qiu,
C.A.Janson,
A.K.Konstantinidis,
S.Nwagwu,
C.Silverman,
W.W.Smith,
S.Khandekar,
J.Lonsdale,
S.S.Abdel-Meguid.
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Ref.
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J Biol Chem, 1999,
274,
36465-36471.
[DOI no: ]
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PubMed id
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Figure 2.
Fig. 2. Overall structure of E. coli FabH . A, ribbon
diagram of the FabH monomer. The N-terminal (1-170) and
C-terminal (171-317) halves have a similar fold. The core
secondary structural elements are labeled as b1-b5 and a1-a3,
respectively and referred in the text with a prefix of N or C to
indicate the domain they belong to. These  -sheet and
 -helices
are drawn in magenta (N, b1-b5), cyan (N, a1-a3), red (C,
b1-b5), and blue (C, a1-a3). N is the N terminus, which precedes
N, b1. C is the C terminus, which comes off C, b5. Secondary
elements of insertion regions are drawn in yellow and orange for
N- and C-terminal domains, respectively. The catalytic Cys112 is
shown in a red ball-and-stick drawing, and the CoA molecule
(green) was taken from the acetyl-CoA complex structure to
orient the view. B, stereo view of the superposition between the
N-terminal (red) and C-terminal (blue) domains of FabH. Core
-strands are
labeled; the overlay was generated by matching the 33 -carbon
pairs from four of the strands.
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Figure 3.
Fig. 3. Ribbon diagram of the FabH dimer. The dimer is
viewed perpendicular to the two-fold axis. One monomer is shown
in yellow and green; the other is shown in cyan and magenta.
Phe^87 and Cys112 (red) are shown as ball-and-stick models.
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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