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| {{STRUCTURE_1bux| PDB=1bux | SCENE= }} | | {{STRUCTURE_1bux| PDB=1bux | SCENE= }} |
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| '''3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE'''
| | ===3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_9786875}}, adds the Publication Abstract to the page |
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| | {{ABSTRACT_PUBMED_9786875}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Pap]] | | [[Category: Pap]] |
| [[Category: Phosphotransferase]] | | [[Category: Phosphotransferase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:59:03 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:45:30 2008'' |