PDBsum entry 2c0t

Transferase

PDB id

2c0t

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Contents

			Protein chains

					428 a.a. *

			Ligands

					L3G ×2

			Metals

					_CA ×4

			Waters ×200

* Residue conservation analysis

PDB id:

2c0t

Links

Name:

Transferase

Title:

Src family kinase hck with bound inhibitor a-641359

Structure:

Tyrosine-protein kinase hck. Chain: a, b. Fragment: sh3-sh2-sh1, residues 80-525. Synonym: haematopoetic cell kinase hck, p59-hck/p60-hck hemopoietic cell kinase. Engineered: yes. Mutation: yes. Other_details: src numbering used. Add 20 to the residue numbers in this entry to obtain actual human hck residue numbers. Residue y501

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell: lymphocyte. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.15Å

R-factor:

0.197

R-free:

0.253

Authors:

D.W.Borhani,A.Burchat,D.J.Calderwood,G.C.Hirst,B.Li,A.Loew

Key ref:

A.Burchat et al. (2006). Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection. Bioorg Med Chem Lett, 16, 118-122. PubMed id: 16216497 DOI: 10.1016/j.bmcl.2005.09.039

Date:

07-Sep-05

Release date:

20-Sep-06

PROCHECK

	Headers

	References

Protein chains

P08631 (HCK_HUMAN) - Tyrosine-protein kinase HCK from Homo sapiens

Seq: Struc:

Seq: Struc:					526 a.a. 428 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 4 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

E.C.2.7.10.2 - non-specific protein-tyrosine kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein]	+	ATP	=	O-phospho-L-tyrosyl-[protein]	+	ADP	+	H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.bmcl.2005.09.039	Bioorg Med Chem Lett 16:118-122 (2006)
PubMed id: 16216497

Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection.
A.Burchat, D.W.Borhani, D.J.Calderwood, G.C.Hirst, B.Li, R.F.Stachlewitz.

ABSTRACT

We describe the identification, SAR, and pharmacology of the src-family selective lck inhibitor A-770041 that prolongs the survival of major histocompatibility mismatched allografts in models of solid organ transplant rejection for greater than 65 days.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21119733

F.Grimminger, R.T.Schermuly, and H.A.Ghofrani (2010).
Targeting non-malignant disorders with tyrosine kinase inhibitors.

Nat Rev Drug Discov, 9, 956-970.

18623061

N.K.Banavali, and B.Roux (2009).
Flexibility and charge asymmetry in the activation loop of Src tyrosine kinases.

Proteins, 74, 378-389.

18568424

S.S.Bhagwat (2009).
Kinase inhibitors for the treatment of inflammatory and autoimmune disorders.

Purinergic Signal, 5, 107-115.

17962511

A.E.Schade, G.L.Schieven, R.Townsend, A.M.Jankowska, V.Susulic, R.Zhang, H.Szpurka, and J.P.Maciejewski (2008).
Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation.

Blood, 111, 1366-1377.

17240048

G.M.Cheetham, P.A.Charlton, J.M.Golec, and J.R.Pollard (2007).
Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680.

Cancer Lett, 251, 323-329.

16732722

M.Braddock, and C.Murray (2006).
10th anniversary Inflammation and Immune Diseases Drug Discovery and Development Summit. 20-21 March 2006, New Brunswick, USA.

Expert Opin Investig Drugs, 15, 721-727.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.