2AD1

Human Sulfotransferase SULT1C2

Summary for 2AD1

• Entry DOI: 10.2210/pdb2ad1/pdb
• Descriptor: Sulfotransferase 1C2 (2 entities in total)
• Functional Keywords: x-ray crystallography; sulfate conjugation, structural genomics, structural genomics consortium, sgc, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O75897
• Total number of polymer chains: 1
• Total formula weight: 35020.14

Authors

Dong, A.,Dombrovski, L.,Loppnau, P.,Edwards, A.M.,Arrowsmith, C.H.,Weigelt, J.,Sundstrom, M.,Bochkarev, A.,Plotnikov, A.N.,Structural Genomics Consortium (SGC) (deposition date: 2005-07-19, release date: 2005-08-02, Last modification date: 2023-08-23)

Primary citation

Allali-Hassani, A.,Pan, P.W.,Dombrovski, L.,Najmanovich, R.,Tempel, W.,Dong, A.,Loppnau, P.,Martin, F.,Thornton, J.,Thonton, J.,Edwards, A.M.,Bochkarev, A.,Plotnikov, A.N.,Vedadi, M.,Arrowsmith, C.H.
Structural and chemical profiling of the human cytosolic sulfotransferases.
Plos Biol., 5:e97-e97, 2007

PubMed Abstract: The human cytosolic sulfotransfases (hSULTs) comprise a family of 12 phase II enzymes involved in the metabolism of drugs and hormones, the bioactivation of carcinogens, and the detoxification of xenobiotics. Knowledge of the structural and mechanistic basis of substrate specificity and activity is crucial for understanding steroid and hormone metabolism, drug sensitivity, pharmacogenomics, and response to environmental toxins. We have determined the crystal structures of five hSULTs for which structural information was lacking, and screened nine of the 12 hSULTs for binding and activity toward a panel of potential substrates and inhibitors, revealing unique "chemical fingerprints" for each protein. The family-wide analysis of the screening and structural data provides a comprehensive, high-level view of the determinants of substrate binding, the mechanisms of inhibition by substrates and environmental toxins, and the functions of the orphan family members SULT1C3 and SULT4A1. Evidence is provided for structural "priming" of the enzyme active site by cofactor binding, which influences the spectrum of small molecules that can bind to each enzyme. The data help explain substrate promiscuity in this family and, at the same time, reveal new similarities between hSULT family members that were previously unrecognized by sequence or structure comparison alone.

PubMed: 17425406
DOI: 10.1371/journal.pbio.0050097

Experimental method

X-RAY DIFFRACTION (2 Å)