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1awo

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(New page: 200px<br /> <applet load="1awo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1awo" /> '''THE SOLUTION NMR STRUCTURE OF ABL SH3 AND I...)
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'''THE SOLUTION NMR STRUCTURE OF ABL SH3 AND ITS RELATIONSHIP TO SH2 IN THE SH(32) CONSTRUCT, 20 STRUCTURES'''<br />
'''THE SOLUTION NMR STRUCTURE OF ABL SH3 AND ITS RELATIONSHIP TO SH2 IN THE SH(32) CONSTRUCT, 20 STRUCTURES'''<br />
==Overview==
==Overview==
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BACKGROUND: The Src homology domains, SH3 and SH2, of Abl protein tyrosine, kinase regulate enzymatic activity in vivo. Abl SH3 suppresses kinase, activity, whereas Abl SH2 is required for the transforming activity of the, activated form of Abl. We expect that the solution structures of Abl SH3, Abl SH2 and Abl SH(32) (a dual domain comprising SH3 and SH2 subdomains), will contribute to a structural basis for understanding the mechanism of, the Abl 'regulatory apparatus'. RESULTS: We present the solution structure, of the free Abl SH3 domain and a structural characterization of the Abl, regulatory apparatus, the SH(32) dual domain. The solution structure of, Abl SH3 was determined using multidimensional double resonance NMR, spectroscopy. It consists of two antiparallel beta sheets packed, orthogonally, an arrangement first shown in spectrin SH3. Compared with, the crystal structure of the Abl SH3 complexed with a natural ligand, there is no significant difference in overall folding pattern. The, structure of the Abl SH(32) dual domain was characterized by NMR, spectroscopy using the 1H and 15N resonance assignment of Abl SH3 and Abl, SH2. On the basis of the high degree of similarity in chemical shifts and, hydrogen/deuterium exchange pattern for the individual domains of SH3 and, SH2 compared with those of the SH(32) dual domain, a structural model of, the Abl SH(32) regulatory apparatus is suggested. This model is in good, agreement with the ligand-binding characteristics of Abl SH3, SH2 and, SH(32). The binding constants for isolated SH3 and SH2 domains when, binding to natural ligands, measured by intrinsic fluorescence quenching, do not differ significantly from the constants of these domains within, SH(32). CONCLUSION: The solution structures of free Abl SH3 and Abl SH2, and the structural model of Abl SH(32), provide information about the, overall topology of these modular domains. The structural model of Abl, SH(32), a monomer, consists of the SH3 and SH2 domains connected by a, flexible linker. Sites of ligand binding for the two subdomains are, independent.
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BACKGROUND: The Src homology domains, SH3 and SH2, of Abl protein tyrosine kinase regulate enzymatic activity in vivo. Abl SH3 suppresses kinase activity, whereas Abl SH2 is required for the transforming activity of the activated form of Abl. We expect that the solution structures of Abl SH3, Abl SH2 and Abl SH(32) (a dual domain comprising SH3 and SH2 subdomains) will contribute to a structural basis for understanding the mechanism of the Abl 'regulatory apparatus'. RESULTS: We present the solution structure of the free Abl SH3 domain and a structural characterization of the Abl regulatory apparatus, the SH(32) dual domain. The solution structure of Abl SH3 was determined using multidimensional double resonance NMR spectroscopy. It consists of two antiparallel beta sheets packed orthogonally, an arrangement first shown in spectrin SH3. Compared with the crystal structure of the Abl SH3 complexed with a natural ligand, there is no significant difference in overall folding pattern. The structure of the Abl SH(32) dual domain was characterized by NMR spectroscopy using the 1H and 15N resonance assignment of Abl SH3 and Abl SH2. On the basis of the high degree of similarity in chemical shifts and hydrogen/deuterium exchange pattern for the individual domains of SH3 and SH2 compared with those of the SH(32) dual domain, a structural model of the Abl SH(32) regulatory apparatus is suggested. This model is in good agreement with the ligand-binding characteristics of Abl SH3, SH2 and SH(32). The binding constants for isolated SH3 and SH2 domains when binding to natural ligands, measured by intrinsic fluorescence quenching, do not differ significantly from the constants of these domains within SH(32). CONCLUSION: The solution structures of free Abl SH3 and Abl SH2, and the structural model of Abl SH(32), provide information about the overall topology of these modular domains. The structural model of Abl SH(32), a monomer, consists of the SH3 and SH2 domains connected by a flexible linker. Sites of ligand binding for the two subdomains are independent.
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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1AWO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AWO OCA].
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1AWO is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AWO OCA].
==Reference==
==Reference==
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:03:01 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:49:02 2008''

Revision as of 09:49, 21 February 2008

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1awo

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THE SOLUTION NMR STRUCTURE OF ABL SH3 AND ITS RELATIONSHIP TO SH2 IN THE SH(32) CONSTRUCT, 20 STRUCTURES

Contents

Overview

BACKGROUND: The Src homology domains, SH3 and SH2, of Abl protein tyrosine kinase regulate enzymatic activity in vivo. Abl SH3 suppresses kinase activity, whereas Abl SH2 is required for the transforming activity of the activated form of Abl. We expect that the solution structures of Abl SH3, Abl SH2 and Abl SH(32) (a dual domain comprising SH3 and SH2 subdomains) will contribute to a structural basis for understanding the mechanism of the Abl 'regulatory apparatus'. RESULTS: We present the solution structure of the free Abl SH3 domain and a structural characterization of the Abl regulatory apparatus, the SH(32) dual domain. The solution structure of Abl SH3 was determined using multidimensional double resonance NMR spectroscopy. It consists of two antiparallel beta sheets packed orthogonally, an arrangement first shown in spectrin SH3. Compared with the crystal structure of the Abl SH3 complexed with a natural ligand, there is no significant difference in overall folding pattern. The structure of the Abl SH(32) dual domain was characterized by NMR spectroscopy using the 1H and 15N resonance assignment of Abl SH3 and Abl SH2. On the basis of the high degree of similarity in chemical shifts and hydrogen/deuterium exchange pattern for the individual domains of SH3 and SH2 compared with those of the SH(32) dual domain, a structural model of the Abl SH(32) regulatory apparatus is suggested. This model is in good agreement with the ligand-binding characteristics of Abl SH3, SH2 and SH(32). The binding constants for isolated SH3 and SH2 domains when binding to natural ligands, measured by intrinsic fluorescence quenching, do not differ significantly from the constants of these domains within SH(32). CONCLUSION: The solution structures of free Abl SH3 and Abl SH2, and the structural model of Abl SH(32), provide information about the overall topology of these modular domains. The structural model of Abl SH(32), a monomer, consists of the SH3 and SH2 domains connected by a flexible linker. Sites of ligand binding for the two subdomains are independent.

Disease

Known diseases associated with this structure: Leukemia, Philadelphia chromosome-positive, resistant to imatinib OMIM:[189980]

About this Structure

1AWO is a Single protein structure of sequence from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct., Gosser YQ, Zheng J, Overduin M, Mayer BJ, Cowburn D, Structure. 1995 Oct 15;3(10):1075-86. PMID:8590002

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