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PDBsum entry 5i6v
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PDB id:
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Hydrolase
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Title:
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Structure of f285s, a cancer-associated mutation of the oncogenic phosphatase shp2
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Structure:
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Tyrosine-protein phosphatase non-receptor type 11. Chain: a, b. Synonym: protein-tyrosine phosphatase 1d,ptp-1d,protein-tyrosine phosphatase 2c,ptp-2c,sh-ptp2,shp2,sh-ptp3. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn11, ptp2c, shptp2. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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1.87Å
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R-factor:
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0.203
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R-free:
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0.232
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Authors:
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X.Xu,S.C.Blacklow
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Key ref:
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J.R.LaRochelle
et al.
(2016).
Structural and Functional Consequences of Three Cancer-Associated Mutations of the Oncogenic Phosphatase SHP2.
Biochemistry,
55,
2269-2277.
PubMed id:
DOI:
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Date:
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16-Feb-16
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Release date:
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13-Apr-16
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PROCHECK
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Headers
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References
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Q06124
(PTN11_HUMAN) -
Tyrosine-protein phosphatase non-receptor type 11 from Homo sapiens
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Seq:
Struc:
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593 a.a.
488 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.3.1.3.48
- protein-tyrosine-phosphatase.
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Reaction:
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O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
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O-phospho-L-tyrosyl-[protein]
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+
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H2O
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=
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L-tyrosyl-[protein]
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+
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phosphate
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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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Biochemistry
55:2269-2277
(2016)
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PubMed id:
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Structural and Functional Consequences of Three Cancer-Associated Mutations of the Oncogenic Phosphatase SHP2.
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J.R.LaRochelle,
M.Fodor,
X.Xu,
I.Durzynska,
L.Fan,
T.Stams,
H.M.Chan,
M.J.LaMarche,
R.Chopra,
P.Wang,
P.D.Fortin,
M.G.Acker,
S.C.Blacklow.
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ABSTRACT
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The proto-oncogene PTPN11 encodes a cytoplasmic protein tyrosine phosphatase,
SHP2, which is required for normal development and sustained activation of the
Ras-MAPK signaling pathway. Germline mutations in SHP2 cause developmental
disorders, and somatic mutations have been identified in childhood and adult
cancers and drive leukemia in mice. Despite our knowledge of the PTPN11
variations associated with pathology, the structural and functional consequences
of many disease-associated mutants remain poorly understood. Here, we combine
X-ray crystallography, small-angle X-ray scattering, and biochemistry to
elucidate structural and mechanistic features of three cancer-associated SHP2
variants harboring single point mutations within the N-SH2:PTP interdomain
autoinhibitory interface. Our findings directly compare the impact of each
mutation on autoinhibition of the phosphatase and advance the development of
structure-guided and mutation-specific SHP2 therapies.
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