Takamasa Teramoto

ERRγ tethers strongly bisphenol A and 4-α-cumylphenol in an induced-fit manner

A receptor-binding assay and X-ray crystal structure analysis demonstrated that the endocrine disruptor bisphenol A (BPA) strongly binds to human estrogen-related receptor gamma (ERRgamma). BPA is well anchored to the ligand-binding pocket, forming hydrogen bonds with its two phenol-hydroxyl groups. In this study, we found that 4-alpha-cumylphenol lacking one of its phenol-hydroxyl groups also binds to ERRgamma very strongly. The 2.0 A crystal structure of the 4-alpha-cumylphenol/ERRgamma complex clearly revealed that ERRgammas Leu345-beta-isopropyl plays a role in the tight binding of 4-alpha-cumylphenol and BPA, rotating in a back-and-forth induced-fit manner.

Crystal structure of human tyrosylprotein sulfotransferase-2 reveals the mechanism of protein tyrosine sulfation reaction

Post-translational protein modification by tyrosine-sulfation plays an important role in extracellular protein-protein interactions. The protein tyrosine sulfation reaction is catalyzed by the Golgi-enzyme called the tyrosylprotein sulfotransferase (TPST). To date, no crystal structure is available for TPST. Detailed mechanism of protein tyrosine sulfation reaction has thus remained unclear. Here we present the first crystal structure of the human TPST isoform 2 (TPST2) complexed with a substrate peptide (C4P5Y3) derived from complement C4 and 3’-phosphoadenosine-5’-phosphate (PAP) at 1.9Å resolution. Structural and complementary mutational analyses revealed the molecular basis for catalysis being an SN2-like in-line displacement mechanism. TPST2 appeared to recognize the C4 peptide in a deep cleft by using a short parallel β-sheet type interaction, and the bound C4P5Y3 forms an L-shaped structure. Surprisingly, the mode of substrate peptide recognition observed in the TPST2 structure resembles that observed for the receptor type tyrosine kinases.

On the similar spatial arrangement of active site residues in PAPS-dependent and phenolic sulfate-utilizing sulfotransferases.

Mammalian sulfotransferases (STs) utilize exclusively the sulfuryl group donor 3′‐phosphoadenosine 5′‐phosphosulfate (PAPS) to catalyze the sulfurylation reactions based on a sequential transfer mechanism. In contrast, the commensal intestinal bacterial arylsulfate sulfotransferases (ASSTs) do not use PAPS as the sulfuryl group donor, but instead catalyze sulfuryl transfer from phenolic sulfate to a phenol via a Ping‐Pong mechanism. Interestingly, structural comparison revealed a similar spatial arrangement of the active site residues as well as the cognate substrates in mouse ST (mSULT1D1) and Escherichia coli CFT073 ASST, despite that their overall structures bear no discernible relationship. These observations suggest that the active sites of PAPS‐dependent SULT1D1 and phenolic sulfate‐utilizing ASST represent an example of convergent evolution.

Crystal structure of mSULT1D1, a mouse catecholamine sulfotransferase

In mammals, sulfonation as mediated by specific cytosolic sulfotransferases (SULTs) plays an important role in the homeostasis of dopamine and other catecholamines. To gain insight into the structural basis for dopamine recognition/binding, we determined the crystal structure of a mouse dopamine‐sulfating SULT, mouse SULT1D1 (mSULT1D1). Data obtained indicated that mSULT1D1 comprises of a single α/β domain with a five‐stranded parallel β‐sheet. In contrast to the structure of the human SULT1A3 (hSULT1A3)‐dopamine complex previously reported, molecular modeling and mutational analysis revealed that a water molecule plays a critical role in the recognition of the amine group of dopamine by mSULT1D1. These results imply differences in substrate binding between dopamine‐sulfating SULTs from different species.

Crystal structure of human tyrosylprotein sulfotransferase

Radical cation salts and charge transfer complexes based on tetrathiafulvalene (TTF) and their derivatives constitute a wide class of organic materials with transport properties ranging from insulating to superconducting. The iron group metal bis(1,2-dicarbollide) complexes [3,3’-M(1,2-C2B9H11)2] (M = Fe, Co, Ni) have been proposed as counterions for synthesis of new radical cation-based molecular materials. Substitution of hydrogen atoms in these complexes for various atoms and groups opens practically unlimited perspectives of their modification. In this report we describe synthesis, crystal structure and electrical conductivity of tetrathiafulvalenium salts of iron bis(dicarbollide) anion [3,3’-Fe(1,2-C2B9H10)2]: (ET)2[3,3’-Fe(1,2-C2B9H11)2] (1) and (TMTTF)[3,3’-Fe(1,2-C2B9H11)2] (2).