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PDBsum entry 2p0c
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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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Catalytic domain of the proto-oncogene tyrosine-protein kinase mer
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Structure:
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Proto-oncogene tyrosine-protein kinase mer. Chain: a, b. Fragment: catalytic domain. Synonym: c-mer, receptor tyrosine kinase mertk. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Tissue: peripheral blood leukocyte. Gene: mertk, mer. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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2.40Å
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R-factor:
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0.208
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R-free:
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0.274
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Authors:
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J.R.Walker,X.Huang,P.J.Finerty Jr.,J.Weigelt,M.Sundstrom, C.H.Arrowsmith,A.M.Edwards,A.Bochkarev,S.Dhe-Paganon,Structural Genomics Consortium (Sgc)
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Key ref:
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X.Huang
et al.
(2009).
Structural insights into the inhibited states of the Mer receptor tyrosine kinase.
J Struct Biol,
165,
88-96.
PubMed id:
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Date:
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28-Feb-07
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Release date:
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08-May-07
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PROCHECK
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Headers
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References
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Q12866
(MERTK_HUMAN) -
Tyrosine-protein kinase Mer from Homo sapiens
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Seq:
Struc:
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999 a.a.
249 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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Enzyme class:
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E.C.2.7.10.1
- receptor 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]
Bound ligand (Het Group name = )
matches with 81.25% similarity
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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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J Struct Biol
165:88-96
(2009)
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PubMed id:
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Structural insights into the inhibited states of the Mer receptor tyrosine kinase.
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X.Huang,
P.Finerty,
J.R.Walker,
C.Butler-Cole,
M.Vedadi,
M.Schapira,
S.A.Parker,
B.E.Turk,
D.A.Thompson,
S.Dhe-Paganon.
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ABSTRACT
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The mammalian ortholog of the retroviral oncogene v-Eyk, and a receptor tyrosine
kinase upstream of antiapoptotic and transforming signals, Mer (MerTK) is a
mediator of the phagocytic process, being involved in retinal and immune cell
clearance and platelet aggregation. Mer knockout mice are viable and are
protected from epinephrine-induced pulmonary thromboembolism and ferric
chloride-induced thrombosis. Mer overexpression, on the other hand, is
associated with numerous carcinomas. Although Mer adaptor proteins and signaling
pathways have been identified, it remains unclear how Mer initiates
phagocytosis. When bound to its nucleotide cofactor, the high-resolution
structure of Mer shows an autoinhibited alphaC-Glu-out conformation with
insertion of an activation loop residue into the active site. Mer complexed with
compound-52 (C52:
2-(2-hydroxyethylamino)-6-(3-chloroanilino)-9-isopropylpurine), a ligand
identified from a focused library, retains its DFG-Asp-in and alphaC-Glu-out
conformation, but acquires other conformational changes. The alphaC helix and
DFGL region is closer to the hinge region and the ethanolamine moiety of C52
binds in the groove formed between Leu593 and Val601 of the P-loop, causing a
compression of the active site pocket. These conformational states reveal the
mechanisms of autoinhibition, the pathophysiological basis of disease-causing
mutations, and a platform for the development of chemical probes.
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Links
