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PDBsum entry 2fbn
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Structural genomics, unknown function
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PDB id
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2fbn
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References listed in PDB file
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Key reference
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Title
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Crystallographic structure of the tetratricopeptide repeat domain of plasmodium falciparum fkbp35 and its molecular interaction with hsp90 c-Terminal pentapeptide.
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Authors
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R.Alag,
N.Bharatham,
A.Dong,
T.Hills,
A.Harikishore,
A.A.Widjaja,
S.G.Shochat,
R.Hui,
H.S.Yoon.
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Ref.
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Protein Sci, 2009,
18,
2115-2124.
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PubMed id
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Abstract
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Plasmodium falciparum FK506-binding protein 35 (PfFKBP35) that binds to FK506
contains a conserved tetratricopeptide repeat (TPR) domain. Several known TPR
domains such as Hop, PPP5, CHIP, and FKBP52 are structurally conserved and are
able to interact with molecular chaperones such as Hsp70/Hsp90. Here, we present
the crystal structure of PfFKBP35-TPR and demonstrate its interaction with Hsp90
C-terminal pentapeptide (MEEVD) by surface plasmon resonance and nuclear
magnetic resonance spectroscopy-based binding studies. Our sequence and
structural analyses reveal that PfFKBP35 is similar to Hop and PPP5 in
possessing all the conserved residues which are important for carboxylate
clamping with Hsp90. Mutational studies were carried out on positively charged
clamp residues that are crucial for binding to carboxylate groups of aspartate,
showing that all the mutated residues are important for Hsp90 binding. Molecular
docking and electrostatic calculations demonstrated that the MEEVD peptide of
Hsp90 can form aspartate clamp unlike FKBP52. Our results provide insightful
information and structural basis about the molecular interaction between
PfFKBP35-TPR and Hsp90.
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