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PDBsum entry 4zq0
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Signaling protein
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PDB id
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4zq0
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Crystal structure of giardia 14-3-3 in complex with the phosphopeptide a8ap
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Structure:
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14-3-3 protein. Chain: a, c, b, d. Synonym: putative 14-3-3 domain protein. Engineered: yes. A8ap phosphopeptide. Chain: e, f, g, h. Engineered: yes
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Source:
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Giardia lamblia p15. Organism_taxid: 658858. Gene: dha2_6430, gsb_6430. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630
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Resolution:
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3.10Å
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R-factor:
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0.207
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R-free:
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0.266
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Authors:
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A.Fiorillo,A.Ilari
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Key ref:
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Y.Cau
et al.
(2015).
Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions.
J Chem Inf Model,
55,
2611-2622.
PubMed id:
DOI:
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Date:
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08-May-15
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Release date:
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30-Mar-16
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PROCHECK
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Headers
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References
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E2RU97
(E2RU97_GIAIC) -
14-3-3 protein from Giardia intestinalis (strain ATCC 50803 / WB clone C6)
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Seq:
Struc:
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248 a.a.
234 a.a.
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Key: |
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Secondary structure |
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CATH domain |
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DOI no:
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J Chem Inf Model
55:2611-2622
(2015)
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PubMed id:
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Molecular Dynamics Simulations and Structural Analysis of Giardia duodenalis 14-3-3 Protein-Protein Interactions.
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Y.Cau,
A.Fiorillo,
M.Mori,
A.Ilari,
M.Botta,
M.Lalle.
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ABSTRACT
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Giardiasis is a gastrointestinal diarrheal illness caused by the protozoan
parasite Giardia duodenalis, which affects annually over 200 million people
worldwide. The limited antigiardial drug arsenal and the emergence of clinical
cases refractory to standard treatments dictate the need for new
chemotherapeutics. The 14-3-3 family of regulatory proteins, extensively
involved in protein-protein interactions (PPIs) with pSer/pThr clients,
represents a highly promising target. Despite homology with human counterparts,
the single 14-3-3 of G. duodenalis (g14-3-3) is characterized by a constitutive
phosphorylation in a region critical for target binding, thus affecting the
function and the conformation of g14-3-3/clients interaction. However, to
approach the design of specific small molecule modulators of g14-3-3 PPIs,
structural elucidations are required. Here, we present a detailed computational
and crystallographic study exploring the implications of g14-3-3 phosphorylation
on protein structure and target binding. Self-Guided Langevin Dynamics and
classical molecular dynamics simulations show that phosphorylation affects
locally and globally g14-3-3 conformation, inducing a structural rearrangement
more suitable for target binding. Profitable features for g14-3-3/clients
interaction were highlighted using a hydrophobicity-based descriptor to
characterize g14-3-3 client peptides. Finally, the X-ray structure of g14-3-3 in
complex with a mode-1 prototype phosphopeptide was solved and combined with
structure-based simulations to identify molecular features relevant for clients
binding to g14-3-3. The data presented herein provide a further and structural
understanding of g14-3-3 features and set the basis for drug design studies.
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