1qh4: Difference between revisions

Revision as of 15:39, 21 February 2008

CRYSTAL STRUCTURE OF CHICKEN BRAIN-TYPE CREATINE KINASE AT 1.41 ANGSTROM RESOLUTION

OverviewOverview

Excitable cells and tissues like muscle or brain show a highly fluctuating consumption of ATP, which is efficiently regenerated from a large pool of phosphocreatine by the enzyme creatine kinase (CK). The enzyme exists in tissue--as well as compartment-specific isoforms. Numerous pathologies are related to the CK system: CK is found to be overexpressed in a wide range of solid tumors, whereas functional impairment of CK leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. The crystal structure of chicken cytosolic brain-type creatine kinase (BB-CK) has been solved to 1.41 A resolution by molecular replacement. It represents the most accurately determined structure in the family of guanidino kinases. Except for the N-terminal region (2-12), the structures of both monomers in the biological dimer are very similar and closely resemble those of the other known structures in the family. Specific Ca2+-mediated interactions, found between two dimers in the asymmetric unit, result in structurally independent heterodimers differing in their N-terminal conformation and secondary structure. The high-resolution structure of BB-CK presented in this work will assist in designing new experiments to reveal the molecular basis of the multiple isoform-specific properties of CK, especially regarding different subcellular locations and functional interactions with other proteins. The rather similar fold shared by all known guanidino kinase structures suggests a model for the transition state complex of BB-CK analogous to the one of arginine kinase (AK). Accordingly, we have modeled a putative conformation of CK in the transition state that requires a rigid body movement of the entire N-terminal domain by rms 4 A from the structure without substrates.

About this StructureAbout this Structure

1QH4 is a Single protein structure of sequence from Gallus gallus with and as ligands. Active as Creatine kinase, with EC number 2.7.3.2 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of brain-type creatine kinase at 1.41 A resolution., Eder M, Schlattner U, Becker A, Wallimann T, Kabsch W, Fritz-Wolf K, Protein Sci. 1999 Nov;8(11):2258-69. PMID:10595529

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-[[Image:1qh4.gif|left|200px]]<br /><applet load="1qh4" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1qh4.gif|left|200px]]<br /><applet load="1qh4" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1qh4, resolution 1.41&Aring;" />
 '''CRYSTAL STRUCTURE OF CHICKEN BRAIN-TYPE CREATINE KINASE AT 1.41 ANGSTROM RESOLUTION'''<br />
 ==Overview==
-Excitable cells and tissues like muscle or brain show a highly fluctuating, consumption of ATP, which is efficiently regenerated from a large pool of, phosphocreatine by the enzyme creatine kinase (CK). The enzyme exists in, tissue--as well as compartment-specific isoforms. Numerous pathologies are, related to the CK system: CK is found to be overexpressed in a wide range, of solid tumors, whereas functional impairment of CK leads to a, deterioration in energy metabolism, which is phenotypic for many, neurodegenerative and age-related diseases. The crystal structure of, chicken cytosolic brain-type creatine kinase (BB-CK) has been solved to, 1.41 A resolution by molecular replacement. It represents the most, accurately determined structure in the family of guanidino kinases. Except, for the N-terminal region (2-12), the structures of both monomers in the, biological dimer are very similar and closely resemble those of the other, known structures in the family. Specific Ca2+-mediated interactions, found, between two dimers in the asymmetric unit, result in structurally, independent heterodimers differing in their N-terminal conformation and, secondary structure. The high-resolution structure of BB-CK presented in, this work will assist in designing new experiments to reveal the molecular, basis of the multiple isoform-specific properties of CK, especially, regarding different subcellular locations and functional interactions with, other proteins. The rather similar fold shared by all known guanidino, kinase structures suggests a model for the transition state complex of, BB-CK analogous to the one of arginine kinase (AK). Accordingly, we have, modeled a putative conformation of CK in the transition state that, requires a rigid body movement of the entire N-terminal domain by rms 4 A, from the structure without substrates.
+Excitable cells and tissues like muscle or brain show a highly fluctuating consumption of ATP, which is efficiently regenerated from a large pool of phosphocreatine by the enzyme creatine kinase (CK). The enzyme exists in tissue--as well as compartment-specific isoforms. Numerous pathologies are related to the CK system: CK is found to be overexpressed in a wide range of solid tumors, whereas functional impairment of CK leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. The crystal structure of chicken cytosolic brain-type creatine kinase (BB-CK) has been solved to 1.41 A resolution by molecular replacement. It represents the most accurately determined structure in the family of guanidino kinases. Except for the N-terminal region (2-12), the structures of both monomers in the biological dimer are very similar and closely resemble those of the other known structures in the family. Specific Ca2+-mediated interactions, found between two dimers in the asymmetric unit, result in structurally independent heterodimers differing in their N-terminal conformation and secondary structure. The high-resolution structure of BB-CK presented in this work will assist in designing new experiments to reveal the molecular basis of the multiple isoform-specific properties of CK, especially regarding different subcellular locations and functional interactions with other proteins. The rather similar fold shared by all known guanidino kinase structures suggests a model for the transition state complex of BB-CK analogous to the one of arginine kinase (AK). Accordingly, we have modeled a putative conformation of CK in the transition state that requires a rigid body movement of the entire N-terminal domain by rms 4 A from the structure without substrates.
 ==About this Structure==
-QH4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with CA and ACT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Creatine_kinase Creatine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.3.2 2.7.3.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QH4 OCA].
+QH4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ACT:'>ACT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Creatine_kinase Creatine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.3.2 2.7.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QH4 OCA].
 ==Reference==
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 [[Category: neurodegenerative disorders]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 00:41:19 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:39:29 2008''