From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1bux.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1bux.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1bux| PDB=1bux | SCENE= }} | | {{STRUCTURE_1bux| PDB=1bux | SCENE= }} |
| | | | |
| - | '''3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE'''
| + | ===3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | 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 |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9786875 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_9786875}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 31: |
Line 35: |
| | [[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'' |
Revision as of 16:45, 30 June 2008
Template:STRUCTURE 1bux
3'-PHOSPHORYLATED NUCLEOTIDES BINDING TO NUCLEOSIDE DIPHOSPHATE KINASE
Template:ABSTRACT PUBMED 9786875
About this Structure
1BUX is a Single protein structure of sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA.
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:9786875
Page seeded by OCA on Mon Jun 30 19:45:30 2008
