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Figure 1.
Figure 1. PfPK5 Sequence and Fold(A) Alignment of PfPK5
with selected CDKs. PfPK5 (Swissprot accession number Q07785)
was aligned with selected CDK sequences (human CDK2 [P24941], S.
pombe Cdc2 [P04551], S. cerevisiae CDC28 [P00546], H. sapien
CDK6 [Q00534], H. sapien CDK5 [Q00535], and T. brucei tbcrk1
[s05853]), using the program CLUSTAL-W (Thompson et al., 1994),
and rendered with the program Alscript (Barton, 1993) (numbered
as for PfPK5). Key sequence motifs are highlighted: glycines of
the kinase GXGXXG motif, magenta; residues subject to regulatory
phosphorylation in CDK1, red; CDK6 residues that contact
p16^INK4A, light blue (Russo et al., 1998); residues delineating
the activation loop, cyan; residues equivalent to CDK5 153, a
key CDK2/CDK5 sequence difference, salmon (Tarricone et al.,
2001); GDSEID motif, involved in both CKS1 (Bourne et al., 1996)
and KAP binding (Song et al., 2001), dark blue; other residues
that contact KAP or CKS proteins, turquoise; the kinase insert
region, and CDK insert region, areas of hypervariability between
kinases are boxed (Hanks and Hunter, 1995). Residues shaded in
yellow are highly conserved between all CDKs.(B) The monomeric
PfPK5 fold. The N-terminal domain (residues 1-82) is colored
white and the C-terminal domain (residues 83-288) gold. The
glycine-rich loop (residues 10-19), the C helix (residues
39-56), and the activation loop (residues 143-170 from the
conserved DFG to APE motifs) are colored magenta, red, and cyan
respectively. PfPK5 residues Asp125, Asn130, and Asp143 are
drawn in ball-and-stick mode and are discussed in the main
text.(C) Overlay of the structures of monomeric PfPK5Thr198Ala
and CDK2 in the vicinity of the activation loop. CDK2 has been
superimposed, colored green (De Bondt et al., 1993). The CDK2
activation loop forms a b hairpin that turns across the end of
the glycine loop, while the activation loop of PfPK5^Thr198Ala
adopts an extended structure as it stretches away from aL12 into
a short a helix of 2.5 turns.
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