View source for 1bux

[[Image:1bux.gif|left|200px]]

 {{Structure
|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= [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==
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 Structure==
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==
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: Nucleoside-diphosphate kinase]]
[[Category: Single protein]]
[[Category: Deville-Bonne, D.]]
[[Category: Janin, J.]]
[[Category: Schneider, B.]]
[[Category: Veron, M.]]
[[Category: Xu, Y.]]
[[Category: PPS]]
[[Category: inhibitor]]
[[Category: pap]]
[[Category: phosphotransferase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 11:17:54 2008''