Steve Ealick's Research Group


Ralstonia metallidurans Tryptophan 2, 3-dioxygenase


PDB file:

2NOX

Description:

Tryptophan 2,3-dioxygenase (TDO) catalyzes the initial and rate limiting step of the quinolinate biosynthetic pathway, leading to the biosynthesis of the essential redox cofactor NAD. We determined the structure of TDO from Ralstonia metallidurans with the cofactor heme bound in the active site. The enzyme crystallizes in space group P1.

The TDO monomer is an all α-helical structure, consisting of thirteen α-helices and four 310 helices. The core motif of TDO is composed of three long α-helices (α3,α4, and α11), which also form most of the heme binding site. The heme is shown in ball-and-stick at the right.

 

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The R. metallidurans TDO crystal structure contains four tetramers per asymmetric unit. In each tetrame,r the four monomers are related by three mutually perpendicular twofold axes (222 point symmetry). Each molecule has a central channel formed by long helices from each of the four monomers.

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Each active site resides at the interface of two monomers, comprised mostly of one monomer and the N-terminus of the other monomer. A type-b heme molecule is bound at each active site with stacking interactions provided by aromatic residues.

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Reference:

Zhang Y, Kang SA, Mukherjee T, Bale S, Crane BR, Begley TP and Ealick SE. The Crystal Structure and Mechanism of Tryptophan 2,3-Dioxygenase, a Heme Enzyme Involved in Tryptophan Catabolism and in Quinolinate Biosynthesis. Biochemistry 46:145-155 (2007).

 



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