1bux: Difference between revisions

|PDB= 1bux |SIZE=350|CAPTION= <scene name='initialview01'>1bux</scene>, resolution 2.8&Aring;

|SITE=  

|LIGAND= <scene name='pdbligand=PPS:3&#39;-PHOSPHATE-ADENOSINE-5&#39;-PHOSPHATE+SULFATE'>PPS</scene>

|ACTIVITY= <span class='plainlinks'>[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] </span>

|GENE=  

|DOMAIN=

|RELATEDENTRY=

|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bux OCA], [http://www.ebi.ac.uk/pdbsum/1bux PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bux RCSB]</span>

 

 

==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.

 

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].

 

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: Nucleoside-diphosphate kinase]]

[[Category: Single protein]]

[[Category: Deville-Bonne, D.]]

[[Category: Janin, J.]]

[[Category: Schneider, B.]]

[[Category: Veron, M.]]

[[Category: Xu, Y.]]

[[Category: phosphotransferase]]