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Pf-GUK1: Plasmodium falciparum Guanylate Kinase

PDB entry: 1Z6G

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Guanylate kinase (GUK1, also referred to as GMPK) is a nucleoside monophosphate kinase that catalyzes the reversible phosphoryl transfer from ATP to GMP to yield ADP and GDP. GUK1 is also thought to fulfill an essential function in the so-called cGMP cycle regulating the supply of guanine nucleotides to components of signal transduction pathways, possibly p21ras and other G-proteins. In addition to phosphorylating GMP, GUK1 has been shown to play a role in the activation of antiviral prodrugs, such as acyclovir, ganciclovir, and carbovir and anticancer prodrugs such as the thiopurines.

Our 2.2 Å crystal structure of GUK1 from Plasmodium falciparum (PFI1420w) reveals a fold largely similar to extant GUK structures, including the structure from yeast (1EX7) and the one from mouse (1LVG). The sequence of Pf-GUK1 is predicted to have a short, unique low complexity region from position 41 to 49 (RKKREKEKE). This turns out to be a loop in the structure similar to loops in the same region in the other GUK structures.

Materials and Methods