2pey

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{{STRUCTURE_2pey| PDB=2pey | SCENE= }}
{{STRUCTURE_2pey| PDB=2pey | SCENE= }}
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'''Crystal strucutre of deletion mutant of APS-kinase domain of human PAPS-synthetase 1'''
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===Crystal strucutre of deletion mutant of APS-kinase domain of human PAPS-synthetase 1===
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==Overview==
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In mammals, the universal sulfuryl group donor molecule 3'-phosphoadenosine 5'-phosphosulfate (PAPS) is synthesized in two steps by a bifunctional enzyme called PAPS synthetase. The APS kinase domain of PAPS synthetase catalyzes the second step in which APS, the product of the ATP-sulfurylase domain, is phosphorylated on its 3'-hydroxyl group to yield PAPS. The substrate APS acts as a strong uncompetitive inhibitor of the APS kinase reaction. We generated truncated and point mutants of the APS kinase domain that are active but devoid of substrate inhibition. Structural analysis of these mutant enzymes reveals the intrasubunit rearrangements that occur upon substrate binding. We also observe intersubunit rearrangements in this dimeric enzyme that result in asymmetry between the two monomers. Our work elucidates the structural elements required for the ability of the substrate APS to inhibit the reaction at micromolar concentrations. Because the ATP-sulfurylase domain of PAPS synthetase influences these elements in the APS kinase domain, we propose that this could be a communication mechanism between the two domains of the bifunctional enzyme.
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{{ABSTRACT_PUBMED_17540769}}
==About this Structure==
==About this Structure==
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[[Category: Protein-nucleic acid complex]]
[[Category: Protein-nucleic acid complex]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 14 11:38:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:32:03 2008''

Revision as of 00:32, 29 July 2008

Template:STRUCTURE 2pey

Crystal strucutre of deletion mutant of APS-kinase domain of human PAPS-synthetase 1

Template:ABSTRACT PUBMED 17540769

About this Structure

2PEY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural mechanism for substrate inhibition of the adenosine 5'-phosphosulfate kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 and its ramifications for enzyme regulation., Sekulic N, Konrad M, Lavie A, J Biol Chem. 2007 Jul 27;282(30):22112-21. Epub 2007 May 31. PMID:17540769

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