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| - | [[Image:2d06.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2d06| PDB=2d06 | SCENE= }} | | {{STRUCTURE_2d06| PDB=2d06 | SCENE= }} |
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| - | '''Human Sult1A1 Complexed With Pap and estradiol'''
| + | ===Human Sult1A1 Complexed With Pap and estradiol=== |
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| - | ==Overview==
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| - | Human SULT1A1 belongs to the supergene family of sulfotransferases (SULTs) involved in the sulfonation of xeno- and endobiotics. The enzyme is also one of the SULTs responsible for metabolic activation of mutagenic and carcinogenic compounds and therefore is implicated in various cancer forms. Further, it is not well understood how substrate inhibition takes place with rigid fused multiring substrates such as 17beta-estradiol (E2) at high substrate concentrations when subcellular fractions or recombinant enzymes are used. To investigate how estradiol binds to SULT1A1, we co-crystallized SULT1A1 with sulfated estradiol and the cofactor product, PAP (3'-phosphoadenosine 5'-phosphate). The crystal structure of SULT1A1 that we present here has PAP and one molecule of E2 bound in a nonproductive mode in the active site. The structure reveals how the SULT1A1 binding site undergoes conformational changes to accept fused ring substrates such as steroids. In agreement with previous reports, the enzyme shows partial substrate inhibition at high concentrations of E2. A model to explain these kinetics is developed based on the formation of an enzyme x PAP x E2 dead-end complex during catalysis. This model provides a very good quantitative description of the rate versus the [E2] curve. This dead-end complex is proposed to be that described by the observed structure, where E2 is bound in a nonproductive mode.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16221673}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 16221673 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_16221673}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Substrarte inhibition]] | | [[Category: Substrarte inhibition]] |
| | [[Category: Sult 1a1]] | | [[Category: Sult 1a1]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 23:27:20 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 12:36:29 2008'' |
Revision as of 09:36, 27 July 2008
Template:STRUCTURE 2d06
Human Sult1A1 Complexed With Pap and estradiol
Template:ABSTRACT PUBMED 16221673
About this Structure
2D06 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure of human SULT1A1 crystallized with estradiol. An insight into active site plasticity and substrate inhibition with multi-ring substrates., Gamage NU, Tsvetanov S, Duggleby RG, McManus ME, Martin JL, J Biol Chem. 2005 Dec 16;280(50):41482-6. Epub 2005 Oct 12. PMID:16221673
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