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PDBsum entry 2b5h
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Oxidoreductase
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PDB id
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2b5h
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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 mammalian cysteine dioxygenase. A novel mononuclear iron center for cysteine thiol oxidation.
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Authors
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C.R.Simmons,
Q.Liu,
Q.Huang,
Q.Hao,
T.P.Begley,
P.A.Karplus,
M.H.Stipanuk.
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Ref.
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J Biol Chem, 2006,
281,
18723-18733.
[DOI no: ]
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PubMed id
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Abstract
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Cysteine dioxygenase is a mononuclear iron-dependent enzyme responsible for the
oxidation of cysteine with molecular oxygen to form cysteine sulfinate. This
reaction commits cysteine to either catabolism to sulfate and pyruvate or the
taurine biosynthetic pathway. Cysteine dioxygenase is a member of the cupin
superfamily of proteins. The crystal structure of recombinant rat cysteine
dioxygenase has been determined to 1.5-A resolution, and these results confirm
the canonical cupin beta-sandwich fold and the rare cysteinyltyrosine
intramolecular cross-link (between Cys(93) and Tyr(157)) seen in the recently
reported murine cysteine dioxygenase structure. In contrast to the catalytically
inactive mononuclear Ni(II) metallocenter present in the murine structure,
crystallization of a catalytically competent preparation of rat cysteine
dioxygenase revealed a novel tetrahedrally coordinated mononuclear iron center
involving three histidines (His(86), His(88), and His(140)) and a water
molecule. Attempts to acquire a structure with bound ligand using either
cocrystallization or soaking crystals with cysteine revealed the formation of a
mixed disulfide involving Cys(164) near the active site, which may explain
previously observed substrate inhibition. This work provides a framework for
understanding the molecular mechanisms involved in thiol dioxygenation and sets
the stage for exploration of the chemistry of both the novel mononuclear iron
center and the catalytic role of the cysteinyl-tyrosine linkage.
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Figure 1.
FIGURE 1. Electron density evidence for key features of the
CDO active site. 2F[o] - F[c] electron density is shown
contoured at 1.6  . Stick representations
of select protein residues, including the Cys-Tyr linkage, are
shown with iron (orange sphere) and active site waters (red
spheres). All structural figures within this report were
prepared using PyMOL (62).
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Figure 8.
FIGURE 8. Mechanistic proposals for CDO. Scheme A,
mechanistic proposal for the catalytic cycle of cysteine
oxidation. The letter B in this Scheme A indicates a putative
active site base. Scheme B, mechanistic proposal for the single
turnover event generating the cysteinyl-tyrosine thioether
cross-link. Each mechanism is discussed in the text (see
"Discussion").
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
18723-18733)
copyright 2006.
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