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PDBsum entry 1c9y
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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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Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and l-Norvaline at 1.9 a resolution.
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Authors
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D.Shi,
H.Morizono,
M.Aoyagi,
M.Tuchman,
N.M.Allewell.
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Ref.
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Proteins, 2000,
39,
271-277.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of human ornithine transcarbamylase (OTCase) complexed
with carbamoyl phosphate (CP) and L-norvaline (NOR) has been determined to 1.9-A
resolution. There are significant differences in the interactions of CP with the
protein, compared with the interactions of the CP moiety of the bisubstrate
analogue N-(phosphonoacetyl)-L-ornithine (PALO). The carbonyl plane of CP
rotates about 60 degrees compared with the equivalent plane in PALO complexed
with OTCase. This positions the side chain of NOR optimally to interact with the
carbonyl carbon of CP. The mixed-anhydride oxygen of CP, which is analogous to
the methylene group in PALO, interacts with the guanidinium group of Arg-92; the
primary carbamoyl nitrogen interacts with the main-chain carbonyl oxygens of
Cys-303 and Leu-304, the side chain carbonyl oxygen of Gln-171, and the side
chain of Arg-330. The residues that interact with NOR are similar to the
residues that interact with the ornithine (ORN) moiety of PALO. The side chain
of NOR is well defined and close to the side chain of Cys-303 with the side
chains of Leu-163, Leu-200, Met-268, and Pro-305 forming a hydrophobic wall.
C-delta of NOR is close to the carbonyl oxygen of Leu-304 (3.56 A), S-gamma atom
of Cys-303 (4.19 A), and carbonyl carbon of CP (3.28 A). Even though the
N-epsilon atom of ornithine is absent in this structure, the side chain of NOR
is positioned to enable the N-epsilon of ornithine to donate a hydrogen to the
S-gamma atom of Cys-303 along the reaction pathway. Binding of CP and NOR
promotes domain closure to the same degree as PALO, and the active site
structure of CP-NOR-enzyme complex is similar to that of the PALO-enzyme
complex. The structures of the active sites in the complexes of aspartate
transcarbamylase (ATCase) with various substrates or inhibitors are similar to
this OTCase structure, consistent with their common evolutionary origin.
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Figure 1.
Figure 1. Schematic drawing of the reaction catalyzed by OTCase.
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Figure 6.
Figure 6. Schematic drawing of the proposed catalytic mechanism.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2000,
39,
271-277)
copyright 2000.
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