1ov4
From Proteopedia
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|PDB= 1ov4 |SIZE=350|CAPTION= <scene name='initialview01'>1ov4</scene>, resolution 2.7Å | |PDB= 1ov4 |SIZE=350|CAPTION= <scene name='initialview01'>1ov4</scene>, resolution 2.7Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=AE2:AETIOCHOLANOLONE'>AE2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Alcohol_sulfotransferase Alcohol sulfotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.2 2.8.2.2] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alcohol_sulfotransferase Alcohol sulfotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.2 2.8.2.2] </span> |
|GENE= SULT2A1 OR STD OR HST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= SULT2A1 OR STD OR HST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1j99|1J99]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ov4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ov4 OCA], [http://www.ebi.ac.uk/pdbsum/1ov4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ov4 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Histidinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609457 609457]], Selective T-cell defect OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176947 176947]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Rhese, P.]] | [[Category: Rhese, P.]] | ||
[[Category: Shi, R.]] | [[Category: Shi, R.]] | ||
| - | [[Category: AE2]] | ||
| - | [[Category: SO4]] | ||
[[Category: alpha/beta fold]] | [[Category: alpha/beta fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:50:45 2008'' |
Revision as of 19:50, 30 March 2008
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| , resolution 2.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | SULT2A1 OR STD OR HST (Homo sapiens) | ||||||
| Activity: | Alcohol sulfotransferase, with EC number 2.8.2.2 | ||||||
| Related: | 1J99
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human DHEA-ST complexed with androsterone
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.
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 Sun Mar 30 22:50:45 2008
