4kpc

<StructureSection load='4kpc' size='340' side='right' caption='[[4kpc]], [[Resolution|resolution]] 2.70&Aring;' scene=''>

<table><tr><td colspan='2'>[[4kpc]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KPC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KPC FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kpc OCA], [http://pdbe.org/4kpc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kpc RCSB], [http://www.ebi.ac.uk/pdbsum/4kpc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kpc ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

BACKGROUND: Nucleoside diphosphate kinase (NDK) is a housekeeping enzyme that plays key roles in nucleotide recycling and homeostasis in trypanosomatids. It is also secreted by the intracellular parasite Leishmania to modulate the host response. These functions make NDK an attractive target for drug design and for studies aiming at a better understanding of the mechanisms mediating host-pathogen interactions. RESULTS: We report the crystal structure and biophysical characterization of the NDK from Leishmania braziliensis (LbNDK). The subunit consists of six alpha-helices along with a core of four beta-strands arranged in a beta2beta3beta1beta4 antiparallel topology order. In contrast to the NDK from L. major, the LbNDK C-terminal extension is partially unfolded. SAXS data showed that LbNDK forms hexamers in solution in the pH range from 7.0 to 4.0, a hydrodynamic behavior conserved in most eukaryotic NDKs. However, DSF assays show that acidification and alkalization decrease the hexamer stability. CONCLUSIONS: Our results support that LbNDK remains hexameric in pH conditions akin to that faced by this enzyme when secreted by Leishmania amastigotes in the parasitophorous vacuoles (pH 4.7 to 5.3). The unusual unfolded conformation of LbNDK C-terminus decreases the surface buried in the trimer interface exposing new regions that might be explored for the development of compounds designed to disturb enzyme oligomerization, which may impair the important nucleotide salvage pathway in these parasites.

 

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== References ==

[[Category: Nucleoside-diphosphate kinase]]

[[Category: Cunha, E M.F]]

[[Category: Giuseppe, P O]]

[[Category: Murakami, M T]]

[[Category: Oliveira, A H.C de]]

[[Category: Santos, C R]]

[[Category: Vieira, P S]]

[[Category: Ndpk superfamily]]

[[Category: Transferase]]