Structural studies of human brain‐type creatine kinase complexed with the ADP–Mg<sup>2+</sup>–NO<sup>3−</sup>–creatine transition‐state analogue complex

Bong, Seoung Min; Moon, Jin Ho; Nam, Ki Hyun; Lee, Ki Seog; Min, Young; Hwang, Kwang Yeon

doi:10.1016/j.febslet.2008.10.039

Cited by 77 publications

(108 citation statements)

References 33 publications

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“…C␣ ϭ 0.54 Å), con- (60). The annelid UcLK-ADP complex shows little of the substratebound character described for other phosphagen kinases.…”

Section: Subunit Structure and Comparison With Homologsmentioning

confidence: 99%

“…Thus, attempts to crystallize UcLK as TSAC yielded only the binary nucleotide complex. Analogously, crystals of multimeric CK have been reported with substrates bound to some subunits but not others (21,60,61). (Such asymmetry was cited as supporting negative cooperativity (61,62), but this argument has been undercut by a glycocyamine kinase structure with both subunits in the closed substrate-bound configuration (19).)…”

Section: Structure Determinationmentioning

confidence: 99%

“…Subdomain 5 brackets the large domain flexible loop (which is not included in the sub- (20,21,60,61) are tightly clustered with a histidine hydrogen bond to the ribose O2Ј. Eight representative substrate-free structures (chicken mitochondrial GgCK mit , bovine retinal CK, human muscle CK, chicken brain GgCK BB , human mitochondrial HsCK mit , rabbit muscle CK, Trypanosoma cruzi AK, and human brain HsCK BB (yellow)) (7, 34, 40, 60, 67, 74 -76) are more loosely clustered over a 2 Å range, about 4 Å from the transition state location.…”

Section: Dynamic Subdomainsmentioning

confidence: 99%

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The Structure of Lombricine Kinase

Bush

Kirillova

Clark

et al. 2011

Journal of Biological Chemistry

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Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309 -317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His 178 . Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.Lombricine, arginine, and creatine kinases (EC 2.7.3) are homologous phosphagen kinases that catalyze the buffering of cellular ATP levels through phosphoryl transfer to/from their respective guanidino-containing substrates. The reaction is central to short-term temporal energy buffering (1, 2) as well as in spatial shuttling of energy from production to consumption sites (3-5). A wide array of endergonic processes is driven by nucleotide hydrolysis, from motion in molecular motors, active transport, and synthetic metabolism to signal transduction. Thus, the maintenance of a constant ATP/ADP ratio, displaced far from thermodynamic equilibrium in the face of high and variable rates of ATP turnover, is crucial for cellular homeostasis (2).Different organisms use different phosphagen substrates, usually only one and each with its own specific phosphagen kinase ( Fig. 1) (2). Lombricine kinase, as well as taurocyamine kinase and glycocyamine kinase, is found exclusively in annelids and allied groups (2). Phylogenetic analyses and studies of the intron/exon organization of the genes of these phosphagen kinases unique to annelids have shown that they are more closely related to creatine kinases (with which they share 50 -60% sequence identity) than typical monomeric arginine kinases such as that from the horseshoe crab (6) (40% sequence identity). Annelids are more diverse in their choice of phosphagen, and the substrate specificities of the corresponding kinases are often lower (6).Structural work has concentrated on the presumptive ancestral arginine kinase and the vertebrate creatine kinase (7, 8), but sequence alignment suggests that subunit fold, if not quaternary structure, is conserved across the fa...

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“…C␣ ϭ 0.54 Å), con- (60). The annelid UcLK-ADP complex shows little of the substratebound character described for other phosphagen kinases.…”

Section: Subunit Structure and Comparison With Homologsmentioning

confidence: 99%

Section: Structure Determinationmentioning

confidence: 99%

Section: Dynamic Subdomainsmentioning

confidence: 99%

See 1 more Smart Citation

The Structure of Lombricine Kinase

Bush

Kirillova

Clark

et al. 2011

Journal of Biological Chemistry

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“…Hence, for dimeric CKs, a negative intersubunit cooperativity mechanism has been inferred from asymmetric structures of both unliganded and liganded crystal forms (14,19). Similar structural features were reported for a dimeric AK co-crystallized with the pretransition state analog arginine-AMPPNP, which achieved a closed liganded form in a single monomer (5).…”

mentioning

confidence: 59%

“…The C-terminal domain is mainly involved in nucleotide binding and has a consequent inward bending motion when the PK is complexed with an abortive transition state analog (TSA) consisting of the guanidino substrate, the MgADP product, and a trigonal planar nitrate anion that mimics the transferred phosphoryl group (20). The crystal structures of CK-, AK-, and GK-TSA as well as NMR and mass spectrometry studies show that this structural rearrangement is accompanied by the stabilization of a C-terminal flexible loop that shields the active site from the solvent (14,19,20,23,24,27,30,31). The PK-TSA structure is closed, and the bound compounds are locked in proper alignment for the in-line phosphoryl transfer (23,26,(32)(33)(34)).…”

mentioning

confidence: 99%

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni

Merceron

Awama

Montserret

et al. 2015

Journal of Biological Chemistry

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Background: Trematode taurocyamine kinases are contiguous dimers of unknown structure. Results: The first reported crystal structure of taurocyamine kinase displays an original bilobal arrangement compared with true dimeric phosphagen kinases. Conclusion: Each lobe is capable of enzymatic activity and substrate binding in a non-mutually exclusive manner. Significance: This structure can serve as a tool for the rational design of anti-schistosomiasis drugs.

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In Vitro Light‐Up Visualization of a Subunit‐Specific Enzyme by an AIE Probe via Restriction of Single Molecular Motion

Zang

Xie

et al. 2020

Angewandte Chemie

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Enzymes contain several subunits to maintain different biological functions. However, it remains a great challenge for specific discrimination of one subunit over another. Toward this end, the fluorescent probe TPEMA is now presented for highly specific detection of the B subunit of cytosolic creatine (CK) kinase isoenzyme (CK‐B). Owing to its aggregation‐induced emission property, TPEMA shows highly boosted emission toward CK‐B with a fast response time and very low interference from other analytes, including the M subunit of CK (CK‐M). With the aid of a Job plot assay, ITC assay and molecular dynamics simulation, it was directly confirmed that the remarkably enhanced fluorescence of TPEMA in the presence of CK‐B results from the restriction of single molecular motion in the cavity. Selective wash‐free fluorescence imaging of CK‐B in macrophages under different treatments was successfully demonstrated.

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Structural studies of human brain‐type creatine kinase complexed with the ADP–Mg²⁺–NO³⁻–creatine transition‐state analogue complex

Cited by 77 publications

References 33 publications

The Structure of Lombricine Kinase

The Structure of Lombricine Kinase

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni

In Vitro Light‐Up Visualization of a Subunit‐Specific Enzyme by an AIE Probe via Restriction of Single Molecular Motion

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Structural studies of human brain‐type creatine kinase complexed with the ADP–Mg2+–NO3−–creatine transition‐state analogue complex

Cited by 77 publications

References 33 publications

The Structure of Lombricine Kinase

The Structure of Lombricine Kinase

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni

In Vitro Light‐Up Visualization of a Subunit‐Specific Enzyme by an AIE Probe via Restriction of Single Molecular Motion

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Structural studies of human brain‐type creatine kinase complexed with the ADP–Mg²⁺–NO³⁻–creatine transition‐state analogue complex