4PW8

Human tryptophan 2,3-dioxygenase

Summary for 4PW8

• Entry DOI: 10.2210/pdb4pw8/pdb
• Descriptor: Tryptophan 2,3-dioxygenase, COBALT (II) ION (3 entities in total)
• Functional Keywords: dioxygenase, oxidoreductase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 8
• Total formula weight: 353173.34

Authors

Meng, B.,Wu, D.,Gu, J.H.,Ouyang, S.Y.,Ding, W.,Liu, Z.J. (deposition date: 2014-03-19, release date: 2014-08-06, Last modification date: 2023-11-08)

Primary citation

Meng, B.,Wu, D.,Gu, J.,Ouyang, S.,Ding, W.,Liu, Z.J.
Structural and functional analyses of human tryptophan 2,3-dioxygenase
Proteins, 82:3210-3216, 2014

PubMed Abstract: Tryptophan 2,3-dioxygenase (TDO), one of the two key enzymes in the kynurenine pathway, catalyzes the indole ring cleavage at the C2-C3 bond of L-tryptophan. This is a rate-limiting step in the regulation of tryptophan concentration in vivo, and is thus important in drug discovery for cancer and immune diseases. Here, we report the crystal structure of human TDO (hTDO) without the heme cofactor to 2.90 Å resolution. The overall fold and the tertiary assembly of hTDO into a tetramer, as well as the active site architecture, are well conserved and similar to the structures of known orthologues. Kinetic and mutational studies confirmed that eight residues play critical roles in L-tryptophan oxidation.

PubMed: 25066423
DOI: 10.1002/prot.24653

Experimental method

X-RAY DIFFRACTION (2.902 Å)