4ks0

Pyruvate kinase (PYK) from Trypanosoma cruzi in the presence of Magnesium, oxalate and F26BP

spinqualitylabelsall models 4ks0, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ks0 is a 2 chain structure with sequence from Trycc. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FDP, K, MG, OXL Related: 3qv9, 4krz Gene: Tc00.1047053511281.60 (TRYCC) Activity: Pyruvate kinase, with EC number 2.7.1.40 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8 degrees rigid body rocking motion of the A- and C-domain cores in each of the four subunits, coupled with the formation of additional salt bridges across two of the four subunit interfaces. These salt bridges provide increased tetramer stability correlated with an enhanced specificity constant (k cat/S 0.5). A detailed kinetic and structural comparison between the potential drug target PYKs from the pathogenic protists T. cruzi, T. brucei and Leishmania mexicana shows that their allosteric mechanism is conserved. By contrast, a structural comparison of trypanosomatid PYKs with the evolutionarily divergent PYKs of humans and of bacteria shows that they have adopted different allosteric strategies. The underlying principle in each case is to maximize (k cat/S 0.5) by stabilizing and rigidifying the tetramer in an active R-state conformation. However, bacterial and mammalian PYKs have evolved alternative ways of locking the tetramers together. In contrast to the divergent allosteric mechanisms, the PYK active sites are highly conserved across species. Selective disruption of the varied allosteric mechanisms may therefore provide a useful approach for the design of species-specific inhibitors. Structures of pyruvate kinases display evolutionarily divergent allosteric strategies.,Morgan HP, Zhong W, McNae IW, Michels PA, Fothergill-Gilmore LA, Walkinshaw MD R Soc Open Sci. 2014 Sep 24;1(1):140120. doi: 10.1098/rsos.140120. eCollection, 2014 Sep. PMID:26064527 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyruvate Kinase

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