1j99
From Proteopedia
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|PDB= 1j99 |SIZE=350|CAPTION= <scene name='initialview01'>1j99</scene>, resolution 1.99Å | |PDB= 1j99 |SIZE=350|CAPTION= <scene name='initialview01'>1j99</scene>, resolution 1.99Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=AND:3-BETA-HYDROXY-5-ANDROSTEN-17-ONE'>AND</scene>, <scene name='pdbligand=HGI:MERCURY+(II)+IODIDE'>HGI</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j99 OCA], [http://www.ebi.ac.uk/pdbsum/1j99 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1j99 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Dehydroepiandrosterone sulphotransferase (DHEA-ST) is an enzyme that converts dehydroepiandrosterone (DHEA), and some other steroids, into their sulphonated forms. The enzyme catalyses the sulphonation of DHEA on the 3alpha-oxygen, with 3'-phosphoadenosine-5'-phosphosulphate contributing the sulphate. The structure of human DHEA-ST in complex with its preferred substrate DHEA has been solved here to 1.99 A using molecular replacement with oestradiol sulphotransferase (37% sequence identity) as a model. Two alternative substrate-binding orientations have been identified. The primary, catalytic, orientation has the DHEA 3alpha-oxygen and the highly conserved catalytic histidine in nearly identical positions as are seen for the related oestradiol sulphotransferase. The substrate, however, shows rotations of up to 30 degrees, and there is a corresponding rearrangement of the protein loops contributing to the active site. This may also reflect the low identity between the two enzymes. The second orientation penetrates further into the active site and can form a potential hydrogen bond with the desulphonated cofactor 3',5'-phosphoadenosine (PAP). This second site contains more van der Waal interactions with hydrophobic residues than the catalytic site and may also reflect the substrate-inhibition site. The PAP position was obtained from the previously solved structure of DHEA-ST co-crystallized with PAP. This latter structure, due to the arrangement of loops within the active site and monomer interactions, cannot bind substrate. The results presented here describe details of substrate binding to DHEA-ST and the potential relationship to substrate inhibition. | Dehydroepiandrosterone sulphotransferase (DHEA-ST) is an enzyme that converts dehydroepiandrosterone (DHEA), and some other steroids, into their sulphonated forms. The enzyme catalyses the sulphonation of DHEA on the 3alpha-oxygen, with 3'-phosphoadenosine-5'-phosphosulphate contributing the sulphate. The structure of human DHEA-ST in complex with its preferred substrate DHEA has been solved here to 1.99 A using molecular replacement with oestradiol sulphotransferase (37% sequence identity) as a model. Two alternative substrate-binding orientations have been identified. The primary, catalytic, orientation has the DHEA 3alpha-oxygen and the highly conserved catalytic histidine in nearly identical positions as are seen for the related oestradiol sulphotransferase. The substrate, however, shows rotations of up to 30 degrees, and there is a corresponding rearrangement of the protein loops contributing to the active site. This may also reflect the low identity between the two enzymes. The second orientation penetrates further into the active site and can form a potential hydrogen bond with the desulphonated cofactor 3',5'-phosphoadenosine (PAP). This second site contains more van der Waal interactions with hydrophobic residues than the catalytic site and may also reflect the substrate-inhibition site. The PAP position was obtained from the previously solved structure of DHEA-ST co-crystallized with PAP. This latter structure, due to the arrangement of loops within the active site and monomer interactions, cannot bind substrate. The results presented here describe details of substrate binding to DHEA-ST and the potential relationship to substrate inhibition. | ||
| - | |||
| - | ==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: Rehse, P H.]] | [[Category: Rehse, P H.]] | ||
[[Category: Zhou, M.]] | [[Category: Zhou, M.]] | ||
| - | [[Category: AND]] | ||
| - | [[Category: HGI]] | ||
| - | [[Category: IOD]] | ||
[[Category: dehydroepiandosterone]] | [[Category: dehydroepiandosterone]] | ||
[[Category: dhea]] | [[Category: dhea]] | ||
[[Category: sulfotransferase]] | [[Category: sulfotransferase]] | ||
| - | ''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 21:30:19 2008'' |
Revision as of 18:30, 30 March 2008
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| , resolution 1.99Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Alcohol sulfotransferase, with EC number 2.8.2.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF HUMAN DEHYDROEPIANDROSTERONE SULFOTRANSFERASE IN COMPLEX WITH SUBSTRATE
Overview
Dehydroepiandrosterone sulphotransferase (DHEA-ST) is an enzyme that converts dehydroepiandrosterone (DHEA), and some other steroids, into their sulphonated forms. The enzyme catalyses the sulphonation of DHEA on the 3alpha-oxygen, with 3'-phosphoadenosine-5'-phosphosulphate contributing the sulphate. The structure of human DHEA-ST in complex with its preferred substrate DHEA has been solved here to 1.99 A using molecular replacement with oestradiol sulphotransferase (37% sequence identity) as a model. Two alternative substrate-binding orientations have been identified. The primary, catalytic, orientation has the DHEA 3alpha-oxygen and the highly conserved catalytic histidine in nearly identical positions as are seen for the related oestradiol sulphotransferase. The substrate, however, shows rotations of up to 30 degrees, and there is a corresponding rearrangement of the protein loops contributing to the active site. This may also reflect the low identity between the two enzymes. The second orientation penetrates further into the active site and can form a potential hydrogen bond with the desulphonated cofactor 3',5'-phosphoadenosine (PAP). This second site contains more van der Waal interactions with hydrophobic residues than the catalytic site and may also reflect the substrate-inhibition site. The PAP position was obtained from the previously solved structure of DHEA-ST co-crystallized with PAP. This latter structure, due to the arrangement of loops within the active site and monomer interactions, cannot bind substrate. The results presented here describe details of substrate binding to DHEA-ST and the potential relationship to substrate inhibition.
About this Structure
1J99 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human dehydroepiandrosterone sulphotransferase in complex with substrate., Rehse PH, Zhou M, Lin SX, Biochem J. 2002 May 15;364(Pt 1):165-71. PMID:11988089
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