1bux: Difference between revisions
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[[Image:1bux.gif|left|200px]] | [[Image:1bux.gif|left|200px]] | ||
'''3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE''' | {{Structure | ||
|PDB= 1bux |SIZE=350|CAPTION= <scene name='initialview01'>1bux</scene>, resolution 2.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PPS:3'-PHOSPHATE-ADENOSINE-5'-PHOSPHATE SULFATE'>PPS</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Nucleoside-diphosphate_kinase Nucleoside-diphosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.6 2.7.4.6] | |||
|GENE= | |||
}} | |||
'''3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1BUX is a [ | 1BUX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BUX OCA]. | ||
==Reference== | ==Reference== | ||
3'-Phosphorylated nucleotides are tight binding inhibitors of nucleoside diphosphate kinase activity., Schneider B, Xu YW, Janin J, Veron M, Deville-Bonne D, J Biol Chem. 1998 Oct 30;273(44):28773-8. PMID:[http:// | 3'-Phosphorylated nucleotides are tight binding inhibitors of nucleoside diphosphate kinase activity., Schneider B, Xu YW, Janin J, Veron M, Deville-Bonne D, J Biol Chem. 1998 Oct 30;273(44):28773-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9786875 9786875] | ||
[[Category: Dictyostelium discoideum]] | [[Category: Dictyostelium discoideum]] | ||
[[Category: Nucleoside-diphosphate kinase]] | [[Category: Nucleoside-diphosphate kinase]] | ||
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[[Category: PPS]] | [[Category: PPS]] | ||
[[Category: inhibitor]] | [[Category: inhibitor]] | ||
[[Category: | [[Category: pap]] | ||
[[Category: phosphotransferase]] | [[Category: phosphotransferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:16:07 2008'' | ||
Revision as of 11:16, 20 March 2008
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| , resolution 2.8Å | |||||||
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| Ligands: | |||||||
| Activity: | Nucleoside-diphosphate kinase, with EC number 2.7.4.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE
OverviewOverview
Nucleoside diphosphate (NDP) kinase catalyzes the phosphorylation of ribo- and deoxyribonucleosides diphosphates into triphosphates. NDP kinase is also involved in malignant tumors and was shown to activate in vitro transcription of the c-myc oncogene by binding to its NHE sequence. The structure of the complex of NDP kinase with bound ADP shows that the nucleotide adopts a different conformation from that observed in other phosphokinases with an internal H bond between the 3'-OH and the beta-O made free by the phosphate transfer. We use intrinsic protein fluorescence to investigate the inhibitory and binding potential of nucleotide analogues phosphorylated in 3'-OH position of the ribose to both wild type and F64W mutant NDP kinase from Dictyostelium discoideum. Due to their 3'-phosphate, 5'-phosphoadenosine 3'-phosphate (PAP) and adenosine 3'-phosphate 5'-phosphosulfate (PAPS) can be regarded as structural analogues of enzyme-bound ADP. The KD of PAPS (10 microM) is three times lower than the KD of ADP. PAPS also acts as a competitive inhibitor toward natural substrates during catalysis, with a KI in agreement with binding data. The crystal structure of the binary complex between Dictyostelium NDP kinase and PAPS was solved at 2.8-A resolution. It shows a new mode of nucleotide binding at the active site with the 3'-phosphate of PAPS located near the catalytic histidine, at the same position as the gamma-phosphate in the transition state. The sulfate group is directed toward the protein surface. PAPS will be useful for the design of high affinity drugs targeted to NDP kinases.
About this StructureAbout this Structure
1BUX is a Single protein structure of sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA.
ReferenceReference
3'-Phosphorylated nucleotides are tight binding inhibitors of nucleoside diphosphate kinase activity., Schneider B, Xu YW, Janin J, Veron M, Deville-Bonne D, J Biol Chem. 1998 Oct 30;273(44):28773-8. PMID:9786875
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