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PDBsum entry 1ibv
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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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Structure and cooperativity of a t-State mutant of histidine decarboxylase from lactobacillus 30a.
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Authors
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S.Worley,
E.Schelp,
A.F.Monzingo,
S.Ernst,
J.D.Robertus.
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Ref.
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Proteins, 2002,
46,
321-329.
[DOI no: ]
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PubMed id
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Abstract
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Histidine decarboxylase (HDC) from Lactobacillus 30a converts histidine to
histamine, a process that enables the bacteria to maintain the optimum pH range
for cell growth. HDC is regulated by pH; it is active at low pH and inactive at
neutral to alkaline pH. The X-ray structure of HDC at pH 8 revealed that a helix
was disordered, resulting in the disruption of the substrate-binding site. The
HDC trimer has also been shown to exhibit cooperative kinetics at neutral pH,
that is, histidine can trigger a T-state to R-state transition. The D53,54N
mutant of HDC has an elevated Km, even at low pH, indicating that the enzyme
assumes the low activity T-state. We have solved the structures of the D53,54N
mutant at low pH, with and without the substrate analog histidine methyl ester
(HME) bound. Structural analysis shows that the apo-D53,54N mutant is in the
inactive or T-state and that binding of the substrate analog induces the enzyme
to adopt the active or R-state. A mechanism for the cooperative transition is
proposed.
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Figure 2.
Figure 2. Binding of HME in the active site of the D53,54N
mutant of HDC. Residues from the right-hand monomer of the
molecular interface are labeled with (  ).
The pyruvoyl moiety (PVL) is part of the left-hand monomer and
is shown bonded to HME. Hydrogen bonds are drawn with dashed
lines.
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Figure 4.
Figure 4. Superposition of the wild-type pH 8 (T-state) and pH
4.8 (R-state) models at the molecular interface shows how the
change in the position of residue E227 affects its interaction
with R64 .
The pH 8 model is shown with light bonds and pH 4.8 model with
dark bonds. In the R-state model, E227 forms ion pair
interactions across the molecular interface with R48 and
R64 .
R64 also
forms an interaction with D231. In the T state, interactions
with E227 are not observed. R64 only
interacts with D231, and R48 is
disordered.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2002,
46,
321-329)
copyright 2002.
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