1zmw: Difference between revisions

Revision as of 17:17, 21 February 2008

Catalytic and ubiqutin-associated domains of MARK2/PAR-1: T208A/S212A inactive double mutant

OverviewOverview

The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause detachment from microtubules in Alzheimer neurofibrillary degeneration. Homologs of MARK2 include Par-1 in C. elegans and Drosophila, which generates embryonic polarity. We report the X-ray structure of the catalytic and ubiquitin-associated domains (UBA) of human MARK2. The activity was altered by mutations in the ATP binding site and/or activation loop. The catalytic domain shows the small and large lobes typical of kinases. The substrate cleft is in an inactive, open conformation in the inactivated and the wild-type structure. The UBA domain is attached via a taut linker to the large lobe of the kinase domain and leans against a hydrophobic patch on the small lobe. The UBA structure is unusual because the orientation of its third helix is inverted, relative to previous structures. Possible implications of the structure for the regulation of kinase activity are discussed.

About this StructureAbout this Structure

1ZMW is a Single protein structure of sequence from Rattus norvegicus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

ReferenceReference

Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1., Panneerselvam S, Marx A, Mandelkow EM, Mandelkow E, Structure. 2006 Feb;14(2):173-83. PMID:16472737

Page seeded by OCA on Thu Feb 21 16:17:10 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1zmw.gif|left|200px]]<br /><applet load="1zmw" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1zmw.gif|left|200px]]<br /><applet load="1zmw" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1zmw, resolution 2.802&Aring;" />
 '''Catalytic and ubiqutin-associated domains of MARK2/PAR-1: T208A/S212A inactive double mutant'''<br />
 ==Overview==
-The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause, detachment from microtubules in Alzheimer neurofibrillary degeneration., Homologs of MARK2 include Par-1 in C. elegans and Drosophila, which, generates embryonic polarity. We report the X-ray structure of the, catalytic and ubiquitin-associated domains (UBA) of human MARK2. The, activity was altered by mutations in the ATP binding site and/or, activation loop. The catalytic domain shows the small and large lobes, typical of kinases. The substrate cleft is in an inactive, open, conformation in the inactivated and the wild-type structure. The UBA, domain is attached via a taut linker to the large lobe of the kinase, domain and leans against a hydrophobic patch on the small lobe. The UBA, structure is unusual because the orientation of its third helix is, inverted, relative to previous structures. Possible implications of the, structure for the regulation of kinase activity are discussed.
+The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause detachment from microtubules in Alzheimer neurofibrillary degeneration. Homologs of MARK2 include Par-1 in C. elegans and Drosophila, which generates embryonic polarity. We report the X-ray structure of the catalytic and ubiquitin-associated domains (UBA) of human MARK2. The activity was altered by mutations in the ATP binding site and/or activation loop. The catalytic domain shows the small and large lobes typical of kinases. The substrate cleft is in an inactive, open conformation in the inactivated and the wild-type structure. The UBA domain is attached via a taut linker to the large lobe of the kinase domain and leans against a hydrophobic patch on the small lobe. The UBA structure is unusual because the orientation of its third helix is inverted, relative to previous structures. Possible implications of the structure for the regulation of kinase activity are discussed.
 ==About this Structure==
-ZMW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZMW OCA].
+ZMW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZMW OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Mandelkow, E.]]
-[[Category: Mandelkow, E.M.]]
+[[Category: Mandelkow, E M.]]
 [[Category: Marx, A.]]
 [[Category: Panneerselvam, S.]]
 [[Category: serine/threonine protein kinase; mark; par-1; kin1; uba domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 07:32:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:17:10 2008''