1ygj

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(New page: 200px<br /><applet load="1ygj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ygj, resolution 2.7&Aring;" /> '''Crystal Structure of ...)
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caption="1ygj, resolution 2.7&Aring;" />
'''Crystal Structure of Pyridoxal Kinase in Complex with Roscovitine and Derivatives'''<br />
'''Crystal Structure of Pyridoxal Kinase in Complex with Roscovitine and Derivatives'''<br />
==Overview==
==Overview==
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Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+. This, constitutes an essential step in the synthesis of pyridoxal 5'-phosphate, (PLP), the active form of vitamin B6, a cofactor for over 140 enzymes., (R)-Roscovitine (CYC202, Seliciclib) is a relatively selective inhibitor, of cyclin-dependent kinases (CDKs), currently evaluated for the treatment, of cancers, neurodegenerative disorders, renal diseases, and several viral, infections. Affinity chromatography investigations have shown that, (R)-roscovitine also interacts with PDXK. To understand this interaction, we determined the crystal structure of PDXK in complex with, (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the, two latter derivatives being designed to bind to PDXK but not to CDKs., Structural analysis revealed that these three roscovitines bind similarly, in the pyridoxal-binding site of PDXK rather than in the anticipated, ATP-binding site. The pyridoxal pocket has thus an unexpected ability to, accommodate molecules different from and larger than pyridoxal. This work, provides detailed structural information on the interactions between PDXK, and roscovitine and analogs. It could also aid in the design of, roscovitine derivatives displaying strict selectivity for either PDXK or, CDKs.
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Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+. This constitutes an essential step in the synthesis of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, a cofactor for over 140 enzymes. (R)-Roscovitine (CYC202, Seliciclib) is a relatively selective inhibitor of cyclin-dependent kinases (CDKs), currently evaluated for the treatment of cancers, neurodegenerative disorders, renal diseases, and several viral infections. Affinity chromatography investigations have shown that (R)-roscovitine also interacts with PDXK. To understand this interaction, we determined the crystal structure of PDXK in complex with (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter derivatives being designed to bind to PDXK but not to CDKs. Structural analysis revealed that these three roscovitines bind similarly in the pyridoxal-binding site of PDXK rather than in the anticipated ATP-binding site. The pyridoxal pocket has thus an unexpected ability to accommodate molecules different from and larger than pyridoxal. This work provides detailed structural information on the interactions between PDXK and roscovitine and analogs. It could also aid in the design of roscovitine derivatives displaying strict selectivity for either PDXK or CDKs.
==About this Structure==
==About this Structure==
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1YGJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with RMC as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Pyridoxal_kinase Pyridoxal kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.35 2.7.1.35] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1YGJ OCA].
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1YGJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with <scene name='pdbligand=RMC:'>RMC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Pyridoxal_kinase Pyridoxal kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.35 2.7.1.35] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YGJ OCA].
==Reference==
==Reference==
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[[Category: Bach, S.]]
[[Category: Bach, S.]]
[[Category: Cao, P.]]
[[Category: Cao, P.]]
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[[Category: Chang, W.R.]]
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[[Category: Chang, W R.]]
[[Category: Ferandin, Y.]]
[[Category: Ferandin, Y.]]
[[Category: Galons, H.]]
[[Category: Galons, H.]]
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[[Category: Jiang, T.]]
[[Category: Jiang, T.]]
[[Category: Koken, M.]]
[[Category: Koken, M.]]
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[[Category: Li, M.H.]]
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[[Category: Li, M H.]]
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[[Category: Liang, D.C.]]
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[[Category: Liang, D C.]]
[[Category: Meijer, L.]]
[[Category: Meijer, L.]]
[[Category: Reinhardt, J.]]
[[Category: Reinhardt, J.]]
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[[Category: n6-methyl-(r)-roscovitine complex]]
[[Category: n6-methyl-(r)-roscovitine complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:05 2008''

Revision as of 14:05, 21 February 2008


1ygj, resolution 2.7Å

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Crystal Structure of Pyridoxal Kinase in Complex with Roscovitine and Derivatives

Overview

Pyridoxal kinase (PDXK) catalyzes the phosphorylation of pyridoxal, pyridoxamine, and pyridoxine in the presence of ATP and Zn2+. This constitutes an essential step in the synthesis of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, a cofactor for over 140 enzymes. (R)-Roscovitine (CYC202, Seliciclib) is a relatively selective inhibitor of cyclin-dependent kinases (CDKs), currently evaluated for the treatment of cancers, neurodegenerative disorders, renal diseases, and several viral infections. Affinity chromatography investigations have shown that (R)-roscovitine also interacts with PDXK. To understand this interaction, we determined the crystal structure of PDXK in complex with (R)-roscovitine, N6-methyl-(R)-roscovitine, and O6-(R)-roscovitine, the two latter derivatives being designed to bind to PDXK but not to CDKs. Structural analysis revealed that these three roscovitines bind similarly in the pyridoxal-binding site of PDXK rather than in the anticipated ATP-binding site. The pyridoxal pocket has thus an unexpected ability to accommodate molecules different from and larger than pyridoxal. This work provides detailed structural information on the interactions between PDXK and roscovitine and analogs. It could also aid in the design of roscovitine derivatives displaying strict selectivity for either PDXK or CDKs.

About this Structure

1YGJ is a Single protein structure of sequence from Ovis aries with as ligand. Active as Pyridoxal kinase, with EC number 2.7.1.35 Full crystallographic information is available from OCA.

Reference

Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives., Tang L, Li MH, Cao P, Wang F, Chang WR, Bach S, Reinhardt J, Ferandin Y, Galons H, Wan Y, Gray N, Meijer L, Jiang T, Liang DC, J Biol Chem. 2005 Sep 2;280(35):31220-9. Epub 2005 Jun 28. PMID:15985434

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