Crystal structure of rabbit muscle creatine kinase<sup>1</sup>

Rao, Jayasimha; Bujacz, G.; Wlodawer, Alexander

doi:10.1016/s0014-5793(98)01355-6

Cited by 131 publications

(26 citation statements)

References 24 publications

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“…Notably, two flexible loops (residues 61–65 and 316–326), which are supposed to participate directly in the binding of substrates, point out away from the catalytic center, leaving a relatively open binding pocket in uMtCK. The overall three-dimensional structure of human uMtCK is very similar to the other known CKs determined in the “open” unliganded mode, such as human MM-CK (PDB entry:1I0E)20 and BB-CK (PDB entry:3DRE)17, chicken sMtCK (PDB entry:1CRK)12 and BB-CK (PDB entry:1QH4)13, rabbit MM-CK (PDB entry:2CRK)11, and bovine BB-CK (PDB entry:1G0W)14.…”

supporting

confidence: 53%

“…To date, in the CK family including human uMtCK10, 13 crystal structures have been reported and can be sorted into three groups according to the substrate binding mode: the ligand-free-form11121314, the ADP-Mg 2+ -complex1516, and the ADP-Mg 2+ ·nitrate·creatine transition-state analogue complex171819. As the first released CK structure of human origin, human uMtCK is structurally ligand-free.…”

mentioning

confidence: 99%

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Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase

Fan

et al. 2016

Sci Rep

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Human ubiquitous mitochondrial creatine kinase (uMtCK) is responsible for the regulation of cellular energy metabolism. To investigate the phosphoryl-transfer mechanism catalyzed by human uMtCK, in this work, molecular dynamic simulations of uMtCK∙ATP-Mg2+∙creatine complex and quantum mechanism calculations were performed to make clear the puzzle. The theoretical studies hereof revealed that human uMtCK utilizes a two-step dissociative mechanism, in which the E227 residue of uMtCK acts as the catalytic base to accept the creatine guanidinium proton. This catalytic role of E227 was further confirmed by our assay on the phosphatase activity. Moreover, the roles of active site residues in phosphoryl transfer reaction were also identified by site directed mutagenesis. This study reveals the structural basis of biochemical activity of uMtCK and gets insights into its phosphoryl transfer mechanism.

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supporting

confidence: 53%

mentioning

confidence: 99%

Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase

Fan

et al. 2016

Sci Rep

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“…The two cytosolic isoforms are almost superimposed in their backbone structures, and each subunit of both proteins composes a small N-terminal domain (NTD) and a large C-terminal domain (CTD). The discrepancy between the structures of MMCK and BBCK is mainly located at the N-terminus and several loops in the CTD [12]–[15].…”

Section: Introductionmentioning

confidence: 95%

Dissimilarity in the Folding of Human Cytosolic Creatine Kinase Isoenzymes

Wang

Gao

et al. 2011

PLoS ONE

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Creatine kinase (CK, EC 2.7.3.2) plays a key role in the energy homeostasis of excitable cells. The cytosolic human CK isoenzymes exist as homodimers (HMCK and HBCK) or a heterodimer (MBCK) formed by the muscle CK subunit (M) and/or brain CK subunit (B) with highly conserved three-dimensional structures composed of a small N-terminal domain (NTD) and a large C-terminal domain (CTD). The isoforms of CK provide a novel system to investigate the sequence/structural determinants of multimeric/multidomain protein folding. In this research, the role of NTD and CTD as well as the domain interactions in CK folding was investigated by comparing the equilibrium and kinetic folding parameters of HMCK, HBCK, MBCK and two domain-swapped chimeric forms (BnMc and MnBc). Spectroscopic results indicated that the five proteins had distinct structural features depending on the domain organizations. MBCK BnMc had the smallest CD signals and the lowest stability against guanidine chloride-induced denaturation. During the biphasic kinetic refolding, three proteins (HMCK, BnMc and MnBc), which contained either the NTD or CTD of the M subunit and similar microenvironments of the Trp fluorophores, refolded about 10-fold faster than HBCK for both the fast and slow phase. The fast folding of these three proteins led to an accumulation of the aggregation-prone intermediate and slowed down the reactivation rate thereby during the kinetic refolding. Our results suggested that the intra- and inter-subunit domain interactions modified the behavior of kinetic refolding. The alternation of domain interactions based on isoenzymes also provides a valuable strategy to improve the properties of multidomain enzymes in biotechnology.

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“…The ligands were removed from the structure since all of the experiments were performed on apo CK homo-dimer. Residues 1-5 were not resolved in the crystal structure and were not built into the CK homo-dimer since the location of these residues varies among CK analogs (Lahiri et al 2002; Rao et al 1998; Shen et al 2001; Tisi et al 2001) and important for interactions with other proteins but not for CK's interaction with ASB9.…”

Section: Methodsmentioning

confidence: 99%

Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer

et al. 2016

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Summary Cullin-RING E3 Ligases (CRLs) are elongated and bowed protein complexes that transfer ubiquitin over 60 Å to proteins targeted for proteasome degradation. One such CRL contains the ankyrin repeat and SOCS box protein 9 (ASB9), which binds to and partially inhibits creatine kinase (CK). While current models for the ASB9-CK complex contain some known interface residues, the overall structure and precise interface of the ASB9-CK complex remains unknown. Through an integrative modeling approach, we report a third generation model that reveals precisely the interface interactions and also fits the shape of the ASB9-CK complex as determined by SAXS. We constructed an atomic model for the entire CK-targeting CRL to uncover dominant modes of motion that could permit ubiquitin transfer. Remarkably, only the correctly docked CK-containing E3 ligase and not incorrectly docked structures permitted close approach of ubiquitin to the CK substrate.

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Crystal structure of rabbit muscle creatine kinase¹

Cited by 131 publications

References 24 publications

Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase

Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase

Dissimilarity in the Folding of Human Cytosolic Creatine Kinase Isoenzymes

Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer

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Crystal structure of rabbit muscle creatine kinase1

Cited by 131 publications

References 24 publications

Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase

Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase

Dissimilarity in the Folding of Human Cytosolic Creatine Kinase Isoenzymes

Model of the Ankyrin and SOCS Box Protein, ASB9, E3 Ligase Reveals a Mechanism for Dynamic Ubiquitin Transfer

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Crystal structure of rabbit muscle creatine kinase¹