1s4e: Difference between revisions

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New page: left|200px<br /><applet load="1s4e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s4e, resolution 2.90Å" /> '''Pyrococcus furiosus ...
 
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[[Image:1s4e.gif|left|200px]]<br /><applet load="1s4e" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1s4e.gif|left|200px]]<br /><applet load="1s4e" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1s4e, resolution 2.90&Aring;" />
caption="1s4e, resolution 2.90&Aring;" />
'''Pyrococcus furiosus galactokinase in complex with galactose, ADP and magnesium'''<br />
'''Pyrococcus furiosus galactokinase in complex with galactose, ADP and magnesium'''<br />


==Overview==
==Overview==
Galactokinase (GalK) catalyses the first step of the Leloir pathway of, galactose metabolism, the ATP-dependent phosphorylation of galactose to, galactose-1-phosphate. In man, defects in galactose metabolism can result, in disorders with severe clinical consequences, and deficiencies in, galactokinase have been linked with the development of cataracts within, the first few months of life. The crystal structure of GalK from, Pyrococcus furiosus in complex with MgADP and galactose has been, determined to 2.9 A resolution to provide insights into the substrate, specificity and catalytic mechanism of the enzyme. The structure consists, of two domains with the active site in a cleft at the domain interface., Inspection of the substrate binding pocket identifies the amino acid, residues involved in galactose and nucleotide binding and points to both, structural and mechanistic similarities with other enzymes of the GHMP, kinase superfamily to which GalK belongs. Comparison of the sequence of, the Gal3p inducer protein, which is related to GalK and which forms part, of the transcriptional activation of the GAL gene cluster in the yeast, Saccharomyces cerevisiae, has led to an understanding of the molecular, basis of galactose and nucleotide recognition. Finally, the structure has, enabled us to further our understanding on the functional consequences of, mutations in human GalK which cause galactosemia.
Galactokinase (GalK) catalyses the first step of the Leloir pathway of galactose metabolism, the ATP-dependent phosphorylation of galactose to galactose-1-phosphate. In man, defects in galactose metabolism can result in disorders with severe clinical consequences, and deficiencies in galactokinase have been linked with the development of cataracts within the first few months of life. The crystal structure of GalK from Pyrococcus furiosus in complex with MgADP and galactose has been determined to 2.9 A resolution to provide insights into the substrate specificity and catalytic mechanism of the enzyme. The structure consists of two domains with the active site in a cleft at the domain interface. Inspection of the substrate binding pocket identifies the amino acid residues involved in galactose and nucleotide binding and points to both structural and mechanistic similarities with other enzymes of the GHMP kinase superfamily to which GalK belongs. Comparison of the sequence of the Gal3p inducer protein, which is related to GalK and which forms part of the transcriptional activation of the GAL gene cluster in the yeast Saccharomyces cerevisiae, has led to an understanding of the molecular basis of galactose and nucleotide recognition. Finally, the structure has enabled us to further our understanding on the functional consequences of mutations in human GalK which cause galactosemia.


==About this Structure==
==About this Structure==
1S4E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus] with GLA, MG and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Galactokinase Galactokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.6 2.7.1.6] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S4E OCA].  
1S4E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus] with <scene name='pdbligand=GLA:'>GLA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Galactokinase Galactokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.6 2.7.1.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S4E OCA].  


==Reference==
==Reference==
Line 14: Line 14:
[[Category: Pyrococcus furiosus]]
[[Category: Pyrococcus furiosus]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Baker, P.J.]]
[[Category: Baker, P J.]]
[[Category: Barynin, V.]]
[[Category: Barynin, V.]]
[[Category: Geus, D.de.]]
[[Category: Geus, D de.]]
[[Category: Glynn, S.E.]]
[[Category: Glynn, S E.]]
[[Category: Hartley, A.]]
[[Category: Hartley, A.]]
[[Category: Oost, J.van.der.]]
[[Category: Oost, J van der.]]
[[Category: Reece, R.J.]]
[[Category: Reece, R J.]]
[[Category: Rice, D.W.]]
[[Category: Rice, D W.]]
[[Category: Sedelnikova, S.E.]]
[[Category: Sedelnikova, S E.]]
[[Category: Timson, D.J.]]
[[Category: Timson, D J.]]
[[Category: Verhees, C.]]
[[Category: Verhees, C.]]
[[Category: ADP]]
[[Category: ADP]]
Line 31: Line 31:
[[Category: p-loop]]
[[Category: p-loop]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 02:05:31 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:53 2008''