1jkn
From Proteopedia
(New page: 200px<br /><applet load="1jkn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jkn" /> '''Solution Structure of the Nudix Enzyme Diade...) |
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| - | [[Image:1jkn.jpg|left|200px]]<br /><applet load="1jkn" size=" | + | [[Image:1jkn.jpg|left|200px]]<br /><applet load="1jkn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1jkn" /> | caption="1jkn" /> | ||
'''Solution Structure of the Nudix Enzyme Diadenosine Tetraphosphate Hydrolase from Lupinus angustifolius Complexed with ATP'''<br /> | '''Solution Structure of the Nudix Enzyme Diadenosine Tetraphosphate Hydrolase from Lupinus angustifolius Complexed with ATP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Ap(4)A hydrolases are Nudix enzymes that regulate intracellular | + | Ap(4)A hydrolases are Nudix enzymes that regulate intracellular dinucleoside polyphosphate concentrations, implicating them in a range of biological events, including heat shock and metabolic stress. We have demonstrated that ATP x MgF(x) can be used to mimic substrates in the binding site of Ap(4)A hydrolase from Lupinus angustifolius and that, unlike previous substrate analogs, it is in slow exchange with the enzyme. The three-dimensional structure of the enzyme complexed with ATP x MgF(x) was solved and shows significant conformational changes. The substrate binding site of L. angustifolius Ap(4)A hydrolase differs markedly from the two previously published Nudix enzymes, ADP-ribose pyrophosphatase and MutT, despite their common fold and the conservation of active site residues. The majority of residues involved in substrate binding are conserved in asymmetrical Ap(4)A hydrolases from pathogenic bacteria, but are absent in their human counterparts, suggesting that it might be possible to generate compounds that target bacterial, but not human, Ap(4)A hydrolases. |
==About this Structure== | ==About this Structure== | ||
| - | 1JKN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lupinus_angustifolius Lupinus angustifolius] with ATP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Bis(5'-nucleosyl)-tetraphosphatase_(asymmetrical) Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.17 3.6.1.17] Full crystallographic information is available from [http:// | + | 1JKN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lupinus_angustifolius Lupinus angustifolius] with <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Bis(5'-nucleosyl)-tetraphosphatase_(asymmetrical) Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.17 3.6.1.17] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JKN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Lupinus angustifolius]] | [[Category: Lupinus angustifolius]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fletcher, J | + | [[Category: Fletcher, J I.]] |
| - | [[Category: Gayler, K | + | [[Category: Gayler, K R.]] |
| - | [[Category: Gooley, P | + | [[Category: Gooley, P R.]] |
[[Category: Maksel, D.]] | [[Category: Maksel, D.]] | ||
| - | [[Category: Swarbrick, J | + | [[Category: Swarbrick, J D.]] |
[[Category: ATP]] | [[Category: ATP]] | ||
[[Category: alpha-beta-alpha sandwich]] | [[Category: alpha-beta-alpha sandwich]] | ||
[[Category: enzyme-substrate complex]] | [[Category: enzyme-substrate complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:23:43 2008'' |
Revision as of 11:23, 21 February 2008
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Solution Structure of the Nudix Enzyme Diadenosine Tetraphosphate Hydrolase from Lupinus angustifolius Complexed with ATP
Overview
Ap(4)A hydrolases are Nudix enzymes that regulate intracellular dinucleoside polyphosphate concentrations, implicating them in a range of biological events, including heat shock and metabolic stress. We have demonstrated that ATP x MgF(x) can be used to mimic substrates in the binding site of Ap(4)A hydrolase from Lupinus angustifolius and that, unlike previous substrate analogs, it is in slow exchange with the enzyme. The three-dimensional structure of the enzyme complexed with ATP x MgF(x) was solved and shows significant conformational changes. The substrate binding site of L. angustifolius Ap(4)A hydrolase differs markedly from the two previously published Nudix enzymes, ADP-ribose pyrophosphatase and MutT, despite their common fold and the conservation of active site residues. The majority of residues involved in substrate binding are conserved in asymmetrical Ap(4)A hydrolases from pathogenic bacteria, but are absent in their human counterparts, suggesting that it might be possible to generate compounds that target bacterial, but not human, Ap(4)A hydrolases.
About this Structure
1JKN is a Single protein structure of sequence from Lupinus angustifolius with as ligand. Active as Bis(5'-nucleosyl)-tetraphosphatase (asymmetrical), with EC number 3.6.1.17 Full crystallographic information is available from OCA.
Reference
The structure of Ap(4)A hydrolase complexed with ATP-MgF(x) reveals the basis of substrate binding., Fletcher JI, Swarbrick JD, Maksel D, Gayler KR, Gooley PR, Structure. 2002 Feb;10(2):205-13. PMID:11839306
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