8VG7

Crystal Structure of T115A Variant of D-Dopachrome Tautomerase (D-DT)

Summary for 8VG7

• Entry DOI: 10.2210/pdb8vg7/pdb
• Descriptor: D-dopachrome decarboxylase (2 entities in total)
• Functional Keywords: truncation, enzyme, cytokine, isomerase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 12563.50

Authors

Parkins, A.,Pilien, A.,Wolff, A.,Thompson, M.C.,Pantouris, G. (deposition date: 2023-12-23, release date: 2024-05-01, Last modification date: 2024-05-22)

Primary citation

Parkins, A.,Pilien, A.V.R.,Wolff, A.M.,Argueta, C.,Vargas, J.,Sadeghi, S.,Franz, A.H.,Thompson, M.C.,Pantouris, G.
The C-terminal Region of D-DT Regulates Molecular Recognition for Protein-Ligand Complexes.
J.Med.Chem., 67:7359-7372, 2024

PubMed Abstract: Systematic analysis of molecular recognition is critical for understanding the biological function of macromolecules. For the immunomodulatory protein D-dopachrome tautomerase (D-DT), the mechanism of protein-ligand interactions is poorly understood. Here, 17 carefully designed protein variants and wild type (WT) D-DT were interrogated with an array of complementary techniques to elucidate the structural basis of ligand recognition. Utilization of a substrate and two selective inhibitors with distinct binding profiles offered previously unseen mechanistic insights into D-DT-ligand interactions. Our results demonstrate that the C-terminal region serves a key role in molecular recognition via regulation of the active site opening, protein-ligand interactions, and conformational flexibility of the pocket's environment. While our study is the first comprehensive analysis of molecular recognition for D-DT, the findings reported herein promote the understanding of protein functionality and enable the design of new structure-based drug discovery projects.

PubMed: 38670943
DOI: 10.1021/acs.jmedchem.4c00177

Experimental method

X-RAY DIFFRACTION (1.24 Å)