NDLI: A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain

Content Provider	PubMed Central
Author	Levinson, Nicholas M. Olga, Kuchment Shen, Kui Young, Matthew A. Michael, Koldobskiy Karplus, Martin Cole, Philip A. Kuriyan, John
Editor	Pawson, Tony
Copyright Year	2006
Abstract	The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML). The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180° with respect to the active conformation, underlies the specificity of the cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in crystal structures of inactive forms of the closely related Src kinases, and imatinib does not inhibit c-Src. We present a structure of the kinase domain of Abl, determined in complex with an ATP–peptide conjugate, in which the protein adopts an inactive conformation that resembles closely that of the Src kinases. An interesting aspect of the Src-like inactive structure, suggested by molecular dynamics simulations and additional crystal structures, is the presence of features that might facilitate the flip of the DFG motif by providing room for the phenylalanine to move and by coordinating the aspartate side chain as it leaves the active site. One class of mutations in BCR–Abl that confers resistance to imatinib appears more likely to destabilize the inactive Src-like conformation than the active or imatinib-bound conformations. Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain.
Related Links	http://dx.doi.org/10.1371/journal.pbio.0040144
Starting Page	144
File Format	PDF
ISSN	15457885
e-ISSN	15457885
Journal	PLoS Biology
Issue Number	5
Volume Number	4
Language	English
Publisher	Public Library of Science
Publisher Date	2006-05-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Agricultural and Biological Sciences(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Biochemistry, Genetics and Molecular Biology Agricultural and Biological Sciences

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans

Correction: Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans

Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling

Abl Is Able to Inhibit Cell Engulfment

Neutralizing Aptamers from Whole-Cell SELEX Inhibit the RET Receptor Tyrosine Kinase

Retraction: Neutralizing Aptamers from Whole-Cell SELEX Inhibit the RET Receptor Tyrosine Kinase

A new method for isolating tyrosine kinase substrates used to identify fish, an SH3 and PX domain-containing protein, and Src substrate.

Tyrosine phosphorylation of Grb2 by Bcr/Abl and epidermal growth factor receptor: a novel regulatory mechanism for tyrosine kinase signaling

Structural Basis for the Regulation Mechanism of the Tyrosine Kinase CapB from Staphylococcus aureus

A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain

Similar Documents

Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans

Correction: Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans

Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling

Abl Is Able to Inhibit Cell Engulfment

Neutralizing Aptamers from Whole-Cell SELEX Inhibit the RET Receptor Tyrosine Kinase

Retraction: Neutralizing Aptamers from Whole-Cell SELEX Inhibit the RET Receptor Tyrosine Kinase

A new method for isolating tyrosine kinase substrates used to identify fish, an SH3 and PX domain-containing protein, and Src substrate.

Tyrosine phosphorylation of Grb2 by Bcr/Abl and epidermal growth factor receptor: a novel regulatory mechanism for tyrosine kinase signaling

Structural Basis for the Regulation Mechanism of the Tyrosine Kinase CapB from Staphylococcus aureus

A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain