5go1: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5go1 is ON HOLD  until Paper Publication
+==Structural, Functional characterization and discovery of novel inhibitors of Leishmania amazonensis Nucleoside Diphosphatase Kinase (NDK)==
+<StructureSection load='5go1' size='340' side='right'caption='[[5go1]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5go1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_amazonensis Leishmania amazonensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GO1 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5go1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5go1 OCA], [https://pdbe.org/5go1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5go1 RCSB], [https://www.ebi.ac.uk/pdbsum/5go1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5go1 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A1Y0DDB3_LEIAM A0A1Y0DDB3_LEIAM]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Nucleoside diphosphate kinases (NDKs) are ubiquitous enzymes that catalyze the transfer of the gamma-phosphate moiety from an NTP donor to an NDP acceptor, crucial for maintaining the cellular level of nucleoside triphosphates (NTPs). The inability of trypanosomatids to synthesize purines de novo and their dependence on the salvage pathway makes NDK an attractive target to develop drugs for the diseases they cause. Here we report the discovery of novel inhibitors for Leishmania NDK based on the structural and functional characterization of purified recombinant NDK from Leishmania amazonensis. Recombinant LaNDK possesses auto-phosphorylation, phosphotransferase and kinase activities with Histidine 117 playing an essential role. LaNDK crystals were grown by hanging drop vapour diffusion method in a solution containing 18% PEG-MME 500, 100 mM Bis-Tris propane pH 6.0 and 50 mM MgCl2. It belongs to the hexagonal space group P6322 with unit cell parameters a = b = 115.18, c = 62.18 A and alpha = beta = 90 degrees , gamma = 120 degrees . The structure solved by molecular replacement methods was refined to crystallographic R-factor and Rfree values of 22.54 and 26.52%, respectively. Molecular docking and dynamics simulation-based virtual screening identified putative binding compounds. Protein inhibition studies of selected hits identified five inhibitors effective at micromolar concentrations. One of the compounds showed ~45% inhibition of Leishmania promastigotes proliferation. Analysis of inhibitor-NDK complexes reveals the mode of their binding, facilitating design of new compounds for optimization of activities as drugs against leishmaniasis.
-Authors: Mishra, A.K., Agnihotri, P., Singh, S.P., Pratap, J.V.
+Discovery of novel inhibitors for Leishmania nucleoside diphosphatase kinase (NDK) based on its structural and functional characterization.,Mishra AK, Singh N, Agnihotri P, Mishra S, Singh SP, Kolli BK, Chang KP, Sahasrabuddhe AA, Siddiqi MI, Pratap JV J Comput Aided Mol Des. 2017 Jun;31(6):547-562. doi: 10.1007/s10822-017-0022-9., Epub 2017 May 27. PMID:28551817<ref>PMID:28551817</ref>
-Description: Structural, Functional characterization and discovery of novel inhibitors of Leishmania amazonensis Nucleoside Diphosphatase Kinase (NDK)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Mishra, A.K]]
+<div class="pdbe-citations 5go1" style="background-color:#fffaf0;"></div>
-[[Category: Agnihotri, P]]
-[[Category: Pratap, J.V]]
+==See Also==
-[[Category: Singh, S.P]]
+*[[Nucleoside diphosphate kinase 3D structures|Nucleoside diphosphate kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Leishmania amazonensis]]
+[[Category: Agnihotri P]]
+[[Category: Mishra AK]]
+[[Category: Pratap JV]]
+[[Category: Singh SP]]