1ov4
From Proteopedia
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| , resolution 2.7Å | |||||||
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| Ligands: | and | ||||||
| Gene: | SULT2A1 OR STD OR HST (Homo sapiens) | ||||||
| Activity: | Alcohol sulfotransferase, with EC number 2.8.2.2 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human DHEA-ST complexed with androsterone
Contents |
Overview
In steroid biosynthesis, human dehydroepiandrosterone sulfotransferase (DHEA-ST) in the adrenals has been reported to catalyze the transfer of the sulfonate group from 3'-phosphoadenosine-5'-phosphosulfate to dehydroepiandrosterone (DHEA). DHEA and its sulfate play roles as steroid precursors; however, the role of the enzyme in the catabolism of androgens is poorly understood. Androsterone sulfate is clinically recognized as one of the major androgen metabolites found in urine. Here it is demonstrated that this enzyme recognizes androsterone (ADT) as a cognate substrate with similar kinetics but a 2-fold specificity and stronger substrate inhibition than DHEA. The structure of human DHEA-ST in complex with ADT has been solved at 2.7 A resolution, confirming ADT recognition. Structural analysis has revealed the binding mode of ADT differs from that of DHEA, despite the similarity of the overall structure between the ADT and the DHEA binary complexes. Our results identify that this human enzyme is an ADT sulfotransferase as well as a DHEA sulfotransferase, implying an important role in steroid homeostasis for the adrenals and liver.
Disease
Known diseases associated with this structure: Histidinemia OMIM:[609457], Selective T-cell defect OMIM:[176947]
About this Structure
1OV4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Identifying androsterone (ADT) as a cognate substrate for human dehydroepiandrosterone sulfotransferase (DHEA-ST) important for steroid homeostasis: structure of the enzyme-ADT complex., Chang HJ, Shi R, Rehse P, Lin SX, J Biol Chem. 2004 Jan 23;279(4):2689-96. Epub 2003 Oct 21. PMID:14573603
Page seeded by OCA on Thu Mar 20 13:15:59 2008
