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PDBsum entry 1is2
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Oxidoreductase
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PDB id
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1is2
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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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Three-Dimensional structure of the flavoenzyme acyl-Coa oxidase-Ii from rat liver, The peroxisomal counterpart of mitochondrial acyl-Coa dehydrogenase.
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Authors
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Y.Nakajima,
I.Miyahara,
K.Hirotsu,
Y.Nishina,
K.Shiga,
C.Setoyama,
H.Tamaoki,
R.Miura.
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Ref.
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J Biochem (tokyo), 2002,
131,
365-374.
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PubMed id
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Abstract
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Acyl-CoA oxidase (ACO) catalyzes the first and rate-determining step of the
peroxisomal beta-oxidation of fatty acids. The crystal structure of ACO-II,
which is one of two forms of rat liver ACO (ACO-I and ACO-II), has been solved
and refined to an R-factor of 20.6% at 2.2-A resolution. The enzyme is a
homodimer, and the polypeptide chain of the subunit is folded into the
N-terminal alpha-domain, beta-domain, and C-terminal alpha-domain. The X-ray
analysis showed that the overall folding of ACO-II less C-terminal 221 residues
is similar to that of medium-chain acyl-CoA dehydrogenase (MCAD). However, the
N-terminal alpha- and beta-domains rotate by 13 with respect to the C-terminal
alpha-domain compared with those in MCAD to give a long and large crevice that
accommodates the cofactor FAD and the substrate acyl-CoA. FAD is bound to the
crevice between the beta- and C-terminal domains with its adenosine diphosphate
portion interacting extensively with the other subunit of the molecule. The
flavin ring of FAD resides at the active site with its si-face attached to the
beta-domain, and is surrounded by active-site residues in a mode similar to that
found in MCAD. However, the residues have weak interactions with the flavin ring
due to the loss of some of the important hydrogen bonds with the flavin ring
found in MCAD. The catalytic residue Glu421 in the C-terminal alpha-domain seems
to be too far away from the flavin ring to abstract the alpha-proton of the
substrate acyl-CoA, suggesting that the C-terminal domain moves to close the
active site upon substrate binding. The pyrimidine moiety of flavin is exposed
to the solvent and can readily be attacked by molecular oxygen, while that in
MCAD is protected from the solvent. The crevice for binding the fatty acyl chain
is 28 A long and 6 A wide, large enough to accommodate the C23 acyl chain.
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