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PDBsum entry 2bxr
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Oxidoreductase
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PDB id
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2bxr
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References listed in PDB file
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Key reference
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Title
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Three-Dimensional structure of human monoamine oxidase a (mao a): relation to the structures of rat mao a and human mao b.
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Authors
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L.De colibus,
M.Li,
C.Binda,
A.Lustig,
D.E.Edmondson,
A.Mattevi.
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Ref.
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Proc Natl Acad Sci U S A, 2005,
102,
12684-12689.
[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
96%.
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Abstract
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The three-dimensional structure of recombinant human monoamine oxidase A (hMAO
A) as its clorgyline-inhibited adduct is described. Although the chain-fold of
hMAO A is similar to that of rat MAO A and human MAO B (hMAO B), hMAO A is
unique in that it crystallizes as a monomer and exhibits the solution
hydrodynamic behavior of a monomeric form rather than the dimeric form of hMAO B
and rat MAO A. hMAO A's active site consists of a single hydrophobic cavity of
approximately 550 A3, which is smaller than that determined from the structure
of deprenyl-inhibited hMAO B (approximately 700 A3) but larger than that of rat
MAO A (approximately 450 A3). An important component of the active site
structure of hMAO A is the loop conformation of residues 210-216, which differs
from that of hMAO B and rat MAO A. The origin of this structural alteration is
suggested to result from long-range interactions in the monomeric form of the
enzyme. In addition to serving as a basis for the development of hMAO A specific
inhibitors, these data support the proposal that hMAO A involves a change from
the dimeric to the monomeric form through a Glu-151 --> Lys mutation that is
specific of hMAO A [Andrès, A. M., Soldevila, M., Navarro, A., Kidd, K. K.,
Oliva, B. & Bertranpetit, J. (2004) Hum. Genet. 115, 377-386]. These
considerations put into question the use of MAO A from nonhuman sources in drug
development for use in humans.
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Figure 3.
Fig. 3. Stereo closed-up view of the clorgyline site in
hMAO A. Atom colors are as in Fig. 1. The backbone trace of loop
210-216 is shown as a coil.
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Figure 5.
Fig. 5. Active site cavities in hMAO A and hMAO B. (A) The
surface of active site cavity in hMAO A is shown in red
chicken-wire representation in the same orientation as in Fig.
3. Clorgyline is depicted in black. (B) Active site comparison
of hMAO A and hMAO B with the crucial Phe-208 and Ile-335
residues of hMAO A superimposed to the corresponding Ile-199 and
Tyr-326 residues of hMAO B. The protein and inhibitor atoms of
hMAO B are in red. With respect to A, the model has been rotated
by  90° around the
vertical axis in the plane of the drawing. (C) The active site
cavity (red surface) of hMAO B in complex with deprenyl (black)
is depicted in the same orientation as in A.
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