1xnj: Difference between revisions
New page: left|200px<br /> <applet load="1xnj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xnj, resolution 1.98Å" /> '''APS complex of huma... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1xnj.gif|left|200px]]<br /> | [[Image:1xnj.gif|left|200px]]<br /><applet load="1xnj" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1xnj" size=" | |||
caption="1xnj, resolution 1.98Å" /> | caption="1xnj, resolution 1.98Å" /> | ||
'''APS complex of human PAPS synthetase 1'''<br /> | '''APS complex of human PAPS synthetase 1'''<br /> | ||
==Overview== | ==Overview== | ||
The high energy sulfate donor 3'-phosphoadenosine-5-phosphosulfate (PAPS) | The high energy sulfate donor 3'-phosphoadenosine-5-phosphosulfate (PAPS) is used for sulfate conjugation of extracellular matrix, hormones and drugs. Human PAPS synthetase 1 catalyzes two subsequent reactions starting from ATP and sulfate. First the ATP sulfurylase domain forms APS, then the APS kinase domain phosphorylates the APS intermediate to PAPS. Up to now the interaction between the two enzymatic activities remained elusive, mainly because of missing structural information. Here we present the crystal structure of human PAPSS1 at 1.8 angstroms resolution. The structure reveals a homodimeric, asymmetric complex with the shape of a chair. The two kinase domains adopt different conformational states, with only one being able to bind its two substrates. The asymmetric binding of ADP to the APS kinase is not only observed in the crystal structure, but can also be detected in solution, using an enzymatic assay. These observations strongly indicate structural changes during the reaction cycle. Furthermore crystals soaked with ADP and APS could be prepared and the corresponding structures could be solved. | ||
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
1XNJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ADX, ADP and ADX as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1XNJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ADX:'>ADX</scene>, <scene name='pdbligand=ADP:'>ADP</scene> and <scene name='pdbligand=ADX:'>ADX</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XNJ OCA]. | ||
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: Bayer, P.]] | [[Category: Bayer, P.]] | ||
[[Category: Harjes, S.]] | [[Category: Harjes, S.]] | ||
[[Category: Scheidig, A | [[Category: Scheidig, A J.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
[[Category: ADX]] | [[Category: ADX]] | ||
| Line 28: | Line 27: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:56:42 2008'' | ||
Revision as of 16:56, 21 February 2008
|
APS complex of human PAPS synthetase 1
OverviewOverview
The high energy sulfate donor 3'-phosphoadenosine-5-phosphosulfate (PAPS) is used for sulfate conjugation of extracellular matrix, hormones and drugs. Human PAPS synthetase 1 catalyzes two subsequent reactions starting from ATP and sulfate. First the ATP sulfurylase domain forms APS, then the APS kinase domain phosphorylates the APS intermediate to PAPS. Up to now the interaction between the two enzymatic activities remained elusive, mainly because of missing structural information. Here we present the crystal structure of human PAPSS1 at 1.8 angstroms resolution. The structure reveals a homodimeric, asymmetric complex with the shape of a chair. The two kinase domains adopt different conformational states, with only one being able to bind its two substrates. The asymmetric binding of ADP to the APS kinase is not only observed in the crystal structure, but can also be detected in solution, using an enzymatic assay. These observations strongly indicate structural changes during the reaction cycle. Furthermore crystals soaked with ADP and APS could be prepared and the corresponding structures could be solved.
DiseaseDisease
Known disease associated with this structure: SEMD, Pakistani type OMIM:[603005]
About this StructureAbout this Structure
1XNJ is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding., Harjes S, Bayer P, Scheidig AJ, J Mol Biol. 2005 Apr 1;347(3):623-35. Epub 2005 Jan 26. PMID:15755455
Page seeded by OCA on Thu Feb 21 15:56:42 2008