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Title
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Interdomain motion in liver alcohol dehydrogenase. Structural and energetic analysis of the hinge bending mode.
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Authors
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F.Colonna-Cesari,
D.Perahia,
M.Karplus,
H.Eklund,
C.I.Brädén,
O.Tapia.
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Ref.
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J Biol Chem, 1986,
261,
15273-15280.
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PubMed id
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Abstract
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A study of the hinge bending mode in the enzyme liver alcohol dehydrogenase is
made by use of empirical energy functions. The enzyme is a dimer, with each
monomer composed of a coenzyme binding domain and a catalytic domain with a
large cleft between the two. Superposition of the apoenzyme and holoenzyme
crystal structures is used to determine a rigid rotation axis for closing of the
cleft. It is shown that a rigid body transformation of the apoenzyme to the
holoenzyme structure corresponds to a 10 degrees rotation of the catalytic
domain about this axis. The rotation is not along the least-motion path for
closing of the cleft but instead corresponds to the catalytic domain coming
closer to the coenzyme binding domain by a sliding motion. Estimation of the
energy associated with the interdomain motion of the apoenzyme over a range of
90 degrees (-40 to 50 degrees, where 0 degrees corresponds to the minimized
crystal structure) demonstrates that local structural relaxation makes possible
large-scale rotations with relatively small energy increments. A variety of
structural rearrangements associated with the domain motion are characterized.
They involve the hinge region residues that provide the covalent connections
between the two domains and certain loop regions that are brought into contact
by the rotation. Differences between the energy minimized and the holoenzyme
structures point to the existence of alternative conformations for loops and to
the importance of the ligands in the structural rearrangements.
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