4plc

Crystal structure of ancestral apicomplexan lactate dehydrogenase with malate.

spinqualitylabelsall models 4plc, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4plc is a 4 chain structure with sequence from Apicomplexa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: NAD, NAI, PYR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A075B5G8_9APIC Publication Abstract from PubMed Malate and lactate dehydrogenases (MDH and LDH) are homologous, core metabolic enzymes that share a fold and catalytic mechanism yet possess strict specificity for their substrates. In the Apicomplexa, convergent evolution of an unusual LDH from MDH resulted in a difference in substrate preference exceeding 12 orders of magnitude. The molecular and evolutionary mechanisms responsible for this extraordinary functional shift are currently unknown. Using ancestral sequence reconstruction, we find that the evolution of pyruvate specificity in apicomplexan LDHs arose through a classic neofunctionalization mechanism characterized by long-range epistasis, a promiscuous intermediate, and relatively few gain-of-function mutations of large effect. Residues far from the active site determine specificity, as shown by the crystal structures of three ancestral proteins that bracket the key gene duplication event. This work provides an unprecedented atomic-resolution view of evolutionary trajectories resulting in the de novo creation of a nascent enzymatic function. An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases.,Boucher JI, Jacobowitz JR, Beckett BC, Classen S, Theobald DL Elife. 2014 Jun 25:e02304. doi: 10.7554/eLife.02304. PMID:24966208 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Lactate dehydrogenase 3D structures

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