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PDBsum entry 3h0f
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Crystal structure of the human fyn sh3 r96w mutant
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Structure:
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Proto-oncogene tyrosine-protein kinase fyn. Chain: a. Fragment: sh3 domain, unp residues 73-142. Synonym: fyn tyrosine kinase, p59-fyn, protooncogene syn, slk. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: fyn. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.61Å
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R-factor:
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0.209
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R-free:
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0.282
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Authors:
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L.Ponchon,F.Hoh,G.Labesse,C.Dumas,S.T.Arold
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Key ref:
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A.Aldehaiman
et al.
(2021).
Synergy and allostery in ligand binding by HIV-1 Nef.
Biochem J,
478,
1525-1545.
PubMed id:
DOI:
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Date:
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09-Apr-09
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Release date:
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21-Apr-10
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PROCHECK
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Headers
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References
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P06241
(FYN_HUMAN) -
Tyrosine-protein kinase Fyn from Homo sapiens
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Seq:
Struc:
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537 a.a.
59 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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Enzyme class:
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E.C.2.7.10.2
- non-specific protein-tyrosine kinase.
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Reaction:
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L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
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L-tyrosyl-[protein]
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+
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ATP
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=
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O-phospho-L-tyrosyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochem J
478:1525-1545
(2021)
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PubMed id:
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Synergy and allostery in ligand binding by HIV-1 Nef.
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A.Aldehaiman,
A.A.Momin,
A.Restouin,
L.Wang,
X.Shi,
S.Aljedani,
S.Opi,
A.Lugari,
U.F.Shahul Hameed,
L.Ponchon,
X.Morelli,
M.Huang,
C.Dumas,
Y.Collette,
S.T.Arold.
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ABSTRACT
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The Nef protein of human and simian immunodeficiency viruses boosts viral
pathogenicity through its interactions with host cell proteins. By combining the
polyvalency of its large unstructured regions with the binding selectivity and
strength of its folded core domain, Nef can associate with many different host
cell proteins, thereby disrupting their functions. For example, the combination
of a linear proline-rich motif and hydrophobic core domain surface allows Nef to
bind tightly and specifically to SH3 domains of Src family kinases. We
investigated whether the interplay between Nef's flexible regions and its core
domain could allosterically influence ligand selection. We found that the
flexible regions can associate with the core domain in different ways, producing
distinct conformational states that alter the way in which Nef selects for SH3
domains and exposes some of its binding motifs. The ensuing crosstalk between
ligands might promote functionally coherent Nef-bound protein ensembles by
synergizing certain subsets of ligands while excluding others. We also combined
proteomic and bioinformatics analyses to identify human proteins that select SH3
domains in the same way as Nef. We found that only 3% of clones from a
whole-human fetal library displayed Nef-like SH3 selectivity. However, in most
cases, this selectivity appears to be achieved by a canonical linear interaction
rather than by a Nef-like 'tertiary' interaction. Our analysis supports the
contention that Nef's mode of hijacking SH3 domains is a virus-specific
adaptation with no or very few cellular counterparts. Thus, the Nef tertiary
binding surface is a promising virus-specific drug target.
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Links
