Crystal structure of brain-type creatine kinase at 1.41 A resolution. - Archive ouverte HAL Access content directly
Journal Articles Protein Science Year : 1999

Crystal structure of brain-type creatine kinase at 1.41 A resolution.

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Abstract

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.

Dates and versions

inserm-00390826 , version 1 (02-06-2009)

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Michael Eder, Uwe Schlattner, Andreas Becker, Theo Wallimann, Wolfgang Kabsch, et al.. Crystal structure of brain-type creatine kinase at 1.41 A resolution.. Protein Science, 1999, 8 (11), pp.2258-69. ⟨10.1110/ps.8.11.2258⟩. ⟨inserm-00390826⟩

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