A novel structure of an antikinase and its inhibitor

Jacques, DA; Langley, DB; Hynson, RMG; Whitten, AE; Kwan, A; Guss, JM; Trewhella, J

A novel structure of an antikinase and its inhibitor

Jacques, DA

Langley, DB Hynson, RMG Whitten, AE Kwan, A Guss, JM Trewhella, J

Permalink

Publication Type:: Journal Article
Citation:: Journal of Molecular Biology, 2011, 405 (1), pp. 214 - 226
Issue Date:: 2011-01-07

Closed Access

	Filename	Description	Size
	fs.pdf	Published Version	2.49 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Jacques, DA https://orcid.org/0000-0002-6426-4510	en_US
dc.contributor.author	Langley, DB	en_US
dc.contributor.author	Hynson, RMG	en_US
dc.contributor.author	Whitten, AE	en_US
dc.contributor.author	Kwan, A	en_US
dc.contributor.author	Guss, JM	en_US
dc.contributor.author	Trewhella, J	en_US
dc.date.available	2010-10-26	en_US
dc.date.issued	2011-01-07	en_US
dc.identifier.citation	Journal of Molecular Biology, 2011, 405 (1), pp. 214 - 226	en_US
dc.identifier.issn	0022-2836	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116777
dc.description.abstract	In Bacillus subtilis, the KipI protein is a regulator of the phosphorelay governing the onset of sporulation. KipI binds the relevant sensor histidine kinase, KinA, and inhibits the autophosphorylation reaction. Gene homologues of kipI are found almost ubiquitously throughout the bacterial kingdom and are usually located adjacent to, and often fused with, kipA gene homologues. In B. subtilis, the KipA protein inhibits the antikinase activity of KipI thereby permitting sporulation. We have used a combination of biophysical techniques in order to understand the domain structure and shape of the KipI-KipA complex and probe the nature of the interaction. We also have solved the crystal structure of TTHA0988, a Thermus thermophilus protein of unknown function that is homologous to a KipI-KipA fusion. This structure, which is the first to be described for this class of proteins, provides unique insight into the nature of the KipI-KipA complex. The structure confirms that KipI and KipA are proteins with two domains, and the C-terminal domains belong to the cyclophilin family. These cyclophilin domains are positioned in the complex such that their conserved surfaces face each other to form a large "bicyclophilin" cleft. We discuss the sequence conservation and possible roles across species of this near-ubiquitous protein family, which is poorly understood in terms of function. © 2010 Elsevier Ltd All rights reserved.	en_US
dc.relation.ispartof	Journal of Molecular Biology	en_US
dc.relation.isbasedon	10.1016/j.jmb.2010.10.047	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.subject.mesh	Bacillus subtilis	en_US
dc.subject.mesh	Thermus thermophilus	en_US
dc.subject.mesh	Protein Kinases	en_US
dc.subject.mesh	Bacterial Proteins	en_US
dc.subject.mesh	Protein Kinase Inhibitors	en_US
dc.subject.mesh	Crystallography, X-Ray	en_US
dc.subject.mesh	Protein Interaction Mapping	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Protein Binding	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Histidine Kinase	en_US
dc.title	A novel structure of an antikinase and its inhibitor	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	405	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0605 Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	405	en_US

Abstract:

In Bacillus subtilis, the KipI protein is a regulator of the phosphorelay governing the onset of sporulation. KipI binds the relevant sensor histidine kinase, KinA, and inhibits the autophosphorylation reaction. Gene homologues of kipI are found almost ubiquitously throughout the bacterial kingdom and are usually located adjacent to, and often fused with, kipA gene homologues. In B. subtilis, the KipA protein inhibits the antikinase activity of KipI thereby permitting sporulation. We have used a combination of biophysical techniques in order to understand the domain structure and shape of the KipI-KipA complex and probe the nature of the interaction. We also have solved the crystal structure of TTHA0988, a Thermus thermophilus protein of unknown function that is homologous to a KipI-KipA fusion. This structure, which is the first to be described for this class of proteins, provides unique insight into the nature of the KipI-KipA complex. The structure confirms that KipI and KipA are proteins with two domains, and the C-terminal domains belong to the cyclophilin family. These cyclophilin domains are positioned in the complex such that their conserved surfaces face each other to form a large "bicyclophilin" cleft. We discuss the sequence conservation and possible roles across species of this near-ubiquitous protein family, which is poorly understood in terms of function. © 2010 Elsevier Ltd All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/116777