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At least 19 recordsLinked to original sources
PubMed1979

The effects of season and temperature on D-lactate dehydrogenase, pyruvate kinase and arginine kinase in the foot of Helix pomatia L.

The effects of pH, season, environmental and experimental temperatures on the activities and kinetic parameters of D-lactate dehydrogenase, pyruvate kinase and arginine kinase from the foot of the pulmonate snail Helix pomatia were analyzed. Both in phosphate and Tris buffers D-lactate dehydrogenase was the enzyme with the most acid maximum, arginine kinase that with the most alkaline, whilst pyruvate kinase occupied an intermediate position. Pyruvate kinase activity, measured at 20 degrees C, was positively correlated with the environmental temperature at the moment of collecting the animal, whereas neither arginine kinase nor D-lactate dehydrogenase showed such a relationship. A seasonal study based on approximately 100 specimens established that arginine kinase activity remained the same throughout the year. Pyruvate kinase activity was slightly lower, and D-lactate dehydrogenase activity significantly higher, in winter than in summer animals. Snails subjected in spring to a short warm-up period before enzyme extraction showed extreme variability and some extraordinarily high values of pyruvate kinase activity, suggesting that either season or elevated temperature may have an immediate effect on the activity of this enzyme. Individual variability of all three enzymes ranges from 300 to 400%. The activities of pyruvate kinase and D-lactate dehydrogenase are strongly correlated in summer, forming a "constant-proportion-group", whereas in winter, with D-lactate dehydrogenase activity increasing and pyruvate kinase activity decreasing these two enzymes become "uncoupled". The Km value of pyruvate kinase is independent of experimental temperature between 10 and 25 degrees C, whereas that of D-lactate dehydrogenase and arginine kinase increases about three-fold within this range. Thus the temperature relationship of a single enzymic reaction cannot be used as an arguemnt for or against the occurrence of temperature compensation of whole animal metabolism. The possibility of modulation of enzyme activity by environmental temperature is discussed.

Acclimatization↗
PubMed1994

Evolution of phosphagen kinase. Primary structure of glycocyamine kinase and arginine kinase from invertebrates.

Of the six phosphagen kinases found in animals, the primary structure is known only for creatine kinase. Here we report three cDNA-derived or chemically determined amino acid sequences of two kinds of phosphagen kinases: a glycocyamine kinase from the polychaete Neanthes diversicolor (Annelida) and arginine kinase from the abalone Nordotis madaka (Mollusca) and the shrimp Penaeus japonicus (Arthropoda). Like vertebrate creatine kinases are monomers. These enzymes consist of 350 to 390 amino acid residues, and have a calculated molecular mass of 39,900 to 44,500 Da. Neanthes glycocyamine kinase shows 50 to 58% sequence similarity with vertebrate and invertebrate creatine kinases, having the greatest similarity (57 to 58%) with vertebrate mitochondrial creatine kinase isoform. It shows lower, but significant similarity (37 to 39%) with invertebrate arginine kinases. The sequence similarity between Nordotis and Penaeus arginine kinases is 51%. A phylogenetic tree constructed from 14 amino acid sequences of phosphagen kinases showed that they can be separated into three major clusters corresponding to creatine kinase, glycocyamine kinase and arginine kinase. The cluster of glycocyamine kinase is apparently closer to that of creatine kinase than arginine kinase. The cluster of creatine kinase is composed of several subclusters, each corresponding to three vertebrate isoforms and the invertebrate enzyme.

Amino Acid Sequence↗
PubMed1992

Early gene interaction during prepupal expression of Drosophila arginine kinase.

Arginine kinase displays a distinctive rise and fall in specific activity and specific protein levels during the prepupal stage of Drosophila development with maximal activity occurring at morphological stage P3. This developmentally regulated peak is under the influence of ecdysone. Altered doses of the major ecdysone-inducible "early" genes at cytological regions 75B and 2B5 alter this pattern of expression while altered doses of another major "early" gene at 74EF have no effect. We hypothesize that a product of the 2B5 locus and a product of the 75B locus interact to effect this developmental pattern of expression of Drosophila arginine kinase.

Animals↗
PubMed2003

The putative catalytic bases have, at most, an accessory role in the mechanism of arginine kinase.

Arginine kinase is a member of the phosphagen kinase family that includes creatine kinase and likely shares a common reaction mechanism in catalyzing the buffering of cellular ATP energy levels. Abstraction of a proton from the substrate guanidinium by a catalytic base has long been thought to be an early mechanistic step. The structure of arginine kinase as a transition state analog complex (Zhou, G., Somasundaram, T., Blanc, E., Parthasarathy, G., Ellington, W. R., and Chapman, M. S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 8449-8454) showed that Glu-225 and Glu-314 were the only potential catalytic residues contacting the phosphorylated nitrogen. In the present study, these residues were changed to Asp, Gln, and Val or Ala in several single and multisite mutant enzymes. These mutations had little impact on the substrate binding constants. The effect upon activity varied with reductions in kcat between 3000-fold and less than 2-fold. The retention of significant activity in some mutants contrasts with published studies of homologues and suggests that acid-base catalysis by these residues may enhance the rate but is not absolutely essential. Crystal structures of mutant enzymes E314D at 1.9 A and E225Q at 2.8 A resolution showed that the precise alignment of substrates is subtly distorted. Thus, pre-ordering of substrates might be just as important as acid-base chemistry, electrostatics, or other potential effects in the modest impact of these residues upon catalysis.

Amino Acid Substitution↗
PubMed1999

Critical initial real-space refinement in the structure determination of arginine kinase.

Arginine kinase (AK), a homologue of creatine kinase, catalyses the reversible transfer of a phosphoryl group between a guanidino phosphate and ADP. The family of phosphagen kinases eluded structure determination for over 25 years until an inactive form creatine kinase (CK) structure was determined [Fritz-Wolf et al. (1996). Nature (London), 381, 341-345]. The structure determination of the active-form transition-state complex was non-trivial, owing to the distant relatedness and domain reorientation of AK compared with CK. Phases from a molecular-replacement solution of the large domain, supplemented by single isomorphous replacement and inter-crystal averaging, did not reveal interpretable electron density for the small domain. Reciprocal-space refinement of the initial model (Rfree = 0.54) by any of the commonly used methods, including post facto application of maximum-likelihood methods, led to overfitting without significant improvement of the partial initial model. By contrast, in the local real-space refinements which proved successful, the interdependence of atoms is limited to immediate neighbors, and atomic positions are not influenced by errors or omissions in remote parts of the structure. Modest improvement was possible without overfitting, and this was critical to the calculation of improved phases. Phases were refined and extended from 4.0 to 2.5 A resolution by Fourier inversion of omit maps, combination with isomorphous replacement phases and averaging between crystal forms, after several batches of real- and reciprocal-space atomic refinement. The final structure refinement, against a 1.86 A cryo data set yielded a high-quality model with R = 0.196 and Rfree = 0.224.

Arginine Kinase↗
PubMed2003

Functional consequences of a gene duplication and fusion event in an arginine kinase.

Arginine kinase (AK) from the foot of the razor clam Ensis directus consists of two full-length AK domains, denoted D1 and D2, fused in a single polypeptide chain. The full-length cDNA for Ensis AK was obtained and its deduced amino acid sequence was analyzed in the context of the X-ray crystal structure of a typical, monomeric AK. Both domains of Ensis AK contain most of the residues currently thought to be critical in catalysis, suggesting that both AK domains are catalytically competent. The full-length Ensis AK, a D2-NusA-His-tag fusion protein and a D2-truncated AK (enterokinase cleavage product of the fusion protein) were expressed in Escherichia coli and purified. All recombinant AK constructs displayed high enzyme activity. Attempts at expressing active D1 alone, D2 alone or a D1-NusA-His-tag fusion protein were unsuccessful. The catalytic properties of the active proteins were compared with the corresponding properties of recombinant AK from the horseshoe crab Limulus polyphemus, which is a typical monomeric AK. In contrast to expectations, the kinetic results strongly suggest that Ensis AK has only one active domain, namely D2. The K(cat) values for all Ensis constructs were roughly twice that of typical AKs, indicating higher overall catalytic throughput at the competent active site. Furthermore, both the full-length and truncated D2 Ensis AKs showed no synergism of substrate binding unlike typical AKs. The D2-NusA-His-tag fusion construct actually displayed negative synergism of substrate binding, which means that, in effect, the first substrate bound acts as a competitive inhibitor of the second. The conservation of the structure of the apparently inactive D1 may be related to constraints imposed by structural changes that could potentially impact substrate binding in D2 and/or possibly influence the proper folding of the enzyme during synthesis. Overall, the results from the present study indicate that the AK contiguous dimer from Ensis directus functions with activity in only the second domain. Although lacking activity in D1, D2 appears to compensate by having a higher intrinsic catalytic throughput than typical 40-kDa monomeric AKs.

Amino Acid Sequence↗
PubMed1978

The role of creatine kinase and arginine kinase in muscle.

Arginine and creatine kinase activities in different muscles are compared with calculated maximum rates of ATP turnover. The magnitude of the kinase activities decreases in the following order: anaerobic muscles and vertebrate skeletal muscles greater than heart muscle greater than insect flight muscle. The maximum activity of phosphagen kinases (i.e. creatine kinase and arginine kinase), in the direction of phosphagen formation, is lower than the calculated maximum rate of ATP turnover in insect flight muscle or rat heart.

Adenosine Triphosphate↗
PubMed1994

Hybridization of matrix-bound MM-creatine kinase with BB-creatine kinase and arginine kinase.

Dimeric rabbit muscle creatine kinase (MM-CK) was bound to CNBr-activated Sepharose 4B by one of its subunits (MM-CKA). Treatment of MM-CKA with guanidine hydrochloride released the unbound subunit to yield the matrix-bound monomer (M-CKB). M-CKB recombined with dissociated MM-CK soluble subunits to reconstitute a matrix-bound dimer (MM-CKC). M-CKB also associated with dissociated subunits of BB-CK from crude extracts of rabbit brain and of arginine kinase from sea cucumber muscle (MM-AK) to form the matrix-bound heterohybrids MB-CKC and M-CK/M-AKC, respectively. Guanidine hydrochloride gradient elution studies showed that MM-CKA, MM-CKC and MB-CKC were all dissociated at the same concentration of the denaturant (0.96 M), while the M-CK/M-AKC heterohybrid was less stable, dissociating at 0.5 M. The specific interaction between subunits of echinoderm and mammalian phosphagen kinases to form a hybrid enzyme of dual substrate specificity supports the view that these enzymes had a common evolutionary origin.

Animals↗
PubMed1999

Arginine kinase evolved twice: evidence that echinoderm arginine kinase originated from creatine kinase.

Arginine kinase (AK) was isolated from the longitudinal muscle of the sea cucumber Stichopus japonicus. Unlike the monomeric 40 kDa AKs from molluscs and arthropods, but like the cytoplasmic isoenzymes of vertebrate creatine kinase (CK), the Stichopus enzyme was dimeric. To explore the evolutionary origin of the dimeric AK, we determined its cDNA-derived amino acid sequence of 370 residues. A comparison of the sequence with those of other enzymes belonging to the phosphagen kinase family indicated that the entire amino acid sequence of Stichopus AK is apparently much more similar to vertebrate CKs than to all other AKs. A phylogenetic tree also strongly suggests that the Stichopus AK has evolved from CK. These results support the conclusion that AK evolved at least twice during the evolution of phosphagen kinases: first at an early stage of phosphagen kinase evolution (its descendants are molluscan and arthropod AKs) and secondly from CK later in metazoan evolution. A comparison of the amino acid sequence around the guanidino specificity (GS) region (which is a possible candidate for the guanidine substrate recognition site in the phosphagen kinase family) of the Stichopus enzyme with those of other phosphagen kinases showed that the GS region of the Stichopus enzyme was of the AK type: five amino acid deletions in the flexible loop region that might help to accommodate larger guanidine substrates in the active site. The presence of the AK-type deletions in the Stichopus AK, even though it seems that the enzyme's most immediate ancestor was probably CK, strongly suggests that the GS region has a role in substrate specificity. Stichopus AK and presumably other echinoderm AKs seem to have evolved from the CK gene; the sequence of GS region might have been replaced by the AK type via exon shuffling. The presence of an intron near the GS region in the Stichopus AK gene supports this hypothesis.

Amino Acid Sequence↗
PubMed2000

Expression of arginine kinase enzymatic activity and mRNA in gills of the euryhaline crabs Carcinus maenas and Callinectes sapidus.

Phosphagen kinases catalyze the reversible dephosphorylation of guanidino phosphagens such as phosphocreatine and phosphoarginine, contributing to the restoration of adenosine triphosphate concentrations in cells experiencing high and variable demands on their reserves of high-energy phosphates. The major invertebrate phosphagen kinase, arginine kinase, is expressed in the gills of two species of euryhaline crabs, the blue crab Callinectes sapidus and the shore crab Carcinus maenas, in which energy-requiring functions include monovalent ion transport, acid-base balance, nitrogen excretion and gas exchange. The enzymatic activity of arginine kinase approximately doubles in the ion-transporting gills of C. sapidus, a strong osmoregulator, when the crabs are transferred from high to low salinity, but does not change in C. maenas, a more modest osmoregulator. Amplification and sequencing of arginine kinase cDNA from both species, accomplished by reverse transcription of gill mRNA and the polymerase chain reaction, revealed an open reading frame coding for a 357-amino-acid protein. The predicted amino acid sequences showed a minimum of 75 % identity with arginine kinase sequences of other arthropods. Ten of the 11 amino acid residues believed to participate in arginine binding are completely conserved among the arthropod sequences analyzed. An estimation of arginine kinase mRNA abundance indicated that acclimation salinity has no effect on arginine kinase gene transcription. Thus, the observed enhancement of enzyme activity in C. sapidus probably results from altered translation rates or direct activation of pre-existing enzyme protein.

Amino Acid Sequence↗
PubMed2003

Proteolytic susceptibility of creatine kinase isozymes and arginine kinase.

The time course and dose-response to proteolysis of three dimeric isozymes of creatine kinase, CK-MM (muscle), CK-BB (brain), and CK-MB (heart) and the homologous monomer, arginine kinase were compared. Chymotrypsin and trypsin cause a rapid and significant loss of intact CK-BB, but limited hydrolysis of CK-MM. After 1h of hydrolysis by chymotrypsin, 80% of CK-MM is intact as judged by quantification of monomers after electrophoresis in sodium dodecyl sulfate. While 50% of the intact monomers of CK-MB remain under these conditions, no CK-BB monomers are detected. These results indicate that treatment with chymotrypsin leads to a CK-MB devoid of the B-subunit. When treated with trypsin for 1h, CK-MM is totally resistant to hydrolysis and all CK-BB is highly degraded. However, CK-MB exhibits approximately 90% intact monomers, indicating survival of intact B-subunit in CK-MB. This suggests that heterodimerization of a B-subunit with an M-subunit may have a protective effect against hydrolysis by trypsin. In view of the considerably larger number of potentially tryptic sensitive sites on the muscle isozyme, the resistance of CK-MM and susceptibility of CK-BB dimers to trypsin implies that differences in subunit tertiary structure are a factor in proteolysis of the homodimeric isozymes. Arginine kinase is rapidly degraded by trypsin, but is minimally affected by chymotrypsin. The finding that both a monomeric (arginine kinase) and dimeric (CK-BB) phosphagen kinase are highly susceptible to proteolysis by trypsin indicates that quaternary structure is not, in and of itself, an advantage in resistance to proteolysis. Since both arginine kinase and muscle creatine kinase are resistant to chymotryptic hydrolysis, it seems unlikely that in general, the increased packing density, which may result from dimerization can account for the stability of CK-MM towards trypsin.

Animals↗
PubMed2004

Implications of the role of reactive cystein in arginine kinase: reactivation kinetics of 5,5'-dithiobis-(2-nitrobenzoic acid)-modified arginine kinase reactivated by dithiothreitol.

The reduction of 5,5'-dithiobis-(2-nitrobenzoic acid)-modified arginine kinase by dithiothreitol has been investigated using the kinetic theory of the substrate reaction during modification of enzyme activity. The results show that the modified arginine kinase can be fully reactivated by an excess concentration of dithiothreitol in a monophasic kinetic course. The presence of ATP or the transition-state analog markedly slows the apparent reactivation rate constant, while arginine shows no effect. The results of ultraviolet (UV) difference and intrinsic fluorescence spectra indicate that the substrate arginine-ADP-Mg2+ can induce conformational changes of the modified enzyme but adding NO3- cannot induce further changes that occur with the native enzyme. The reactive cysteines' location and role in the catalysis of arginine kinase are discussed. It is suggested that the cysteine may be located in the hinge region of the two domains of arginine kinase. The reactive cysteine of arginine kinase may play an important role not in the binding to the transition-state analog but in the conformational changes caused by the transition-state analog.

Arginine Kinase↗
PubMed1998

Arginine kinase expression and localization in growth cone migration.

Migrating neuronal growth cones exert traction forces that are generated by ATP-driven F-actin/myosin interactions. Sustained generation of these forces may require an energy supply mediated by the guanidino kinases, creatine kinase and arginine kinase. We cloned and sequenced grasshopper arginine kinase and examined its expression during embryogenesis and its subcellular localization in vivo and in vitro. During the first half of embryogenesis, arginine kinase is expressed selectively in a small percentage of ectodermal cells (dorsal closure cells), in a small percentage of mesodermal cells (muscle pioneers), and throughout the developing CNS. Most of these cell types are motile, including nascent neurons, muscle pioneers, dorsal closure cells, and many CNS glia. Neuroblasts also strongly express arginine kinase; they are nonmotile but are undergoing repeated rounds of (ATP-dependent) mitosis. Arginine kinase is colocalized with F-actin in a narrow band along the leading edges of lamellipodia of migrating glia. In neurons undergoing axonogenesis, arginine kinase is concentrated in growth cones and extends to the tips of filopodia. The amount of arginine kinase varies widely between growth cones, even between different growth cones of the same neuron. Energy for growth cone migration appears to be mobilized by (1) selective expression of arginine kinase by neurons, (2) localization of arginine kinase within growth cones, and (3) concentration of arginine kinase within specific growth cones, depending on the traction forces being generated. Mobilization of guanidino kinases may participate in the selective growth of specific growth cones.

Animals↗
PubMed1976

Effects of arginine and some analogues of the partial adenosine triphosphate-adenosine diphosphate exchange reaction catalysed by arginine kinase. Evolutionary divergence in the mechanism of action of a monomer and a dimer arginine kinase.

1. Both the monomer arginine kinase from lobster muscle and the dimer arginine kinase from Holothuria forskali catalyse the ATP-ADP partial exchange reaction at rates equal to 3 and 0.6% of the normal rate of transphosphorylation respectively. The Mg2+-nucleotide complex is the substrate for this as it is for the kinase reaction. 2. Analogues of arginine inhibit the exchange reaction of the lobster enzyme but enhance that of the Holothuria enzyme. 3. With the lobster enzyme NO3- has no effect on the exchange reaction alone and inhibit only slightly the apparent enhancement of the exchange reaction produced by the addition of arginine. This is compatible with previous findings for this enzyme that formation of the anion-stabilized dead-end complex, enzyme-arginine-MgADP-NO3-, does not occur to any marked degree. 4. About 80% of the ADP-ATP exchange reaction of the lobster enzyme remains after inhibition with iodoacetamide. This is further decreased to 65% by the addition of L-arginine, indicating that this substrate does bind to the thiolmodified enzyme. 5. It is concluded that the partial exchange reaction is a genuine phenomenon not mediated by trace amounts of arginine. From the effects of arginine and related compounds it would appear that during the normal kinase reaction the partial ATP-ADP exchange reaction is suppressed in the lobster enzyme but enhanced in the Holothuria enzyme. This reflects a remarkable evolutionary divergence of two homologous enzymes.

Adenosine Diphosphate↗
PubMed1998

Gene duplication and fusion have occurred frequently in the evolution of phosphagen kinases--a two-domain arginine kinase from the clam Pseudocardium sachalinensis.

In contrast to the 40 kDa arginine kinases from Molllusca and Arthropoda, the adductor muscle of the marine clam Pseudocardium sachalinensis contains an unusual arginine kinase consisting of an 86 kDa subunit. The cDNA encoding the 86 kDa arginine kinase was amplified by PCR and the cDNA-derived amino acid sequence of 724 residues was determined. The exact molecular mass for the protein was calculated to be 80941 Da. The amino acid sequence clearly indicates that Pseudocardium arginine kinase has a two-domain structure: the first domain residues 1-363 and the second domain 364-724. The two domains, which are separated by an intron of 176 bp in the gene, show 62% amino acid sequence identity. This two-domain arginine kinase from a mollusc represents yet another multiple-domain enzyme observed in the phosphagen kinase enzyme family. Two-domain and three-domain enzymes have been observed in three other diverse invertebrate groups. Thus, it is clear that gene duplication and subsequent fusion have occurred frequently, and likely independently, during the course of the evolution of this enzyme family. Comparison of the amino acid sequence in the GS region (a possible candidate for the guanidine substrate recognition site in the phosphagen kinase family) suggests that the first domain of Pseudocardium arginine kinase might not retain a complete enzyme activity, because the Asp-7 in the GS region, which is assumed to be involved in the recognition of the positive charge of arginine, was replaced by a Gly residue in the first domain.

Amino Acid Sequence↗
PubMed2004

Role of amino acid residues on the GS region of Stichopus arginine kinase and Danio creatine kinase.

Stichopus arginine kinase (AK) is a unique enzyme in that it evolved not from the AK gene but from the creatine kinase (CK) gene: the entire amino acid sequence is homologous with other CKs apart from the guanidine specificity region (GS region), which is identical in structure to that of AK. Ten independent mutations were introduced around the GS region in Stichopus AK. When an insertion or deletion was introduced near the GS region, the Vmax of the mutant enzyme was dramatically decreased to less than 0.1% of the wild type, suggesting that the length of the GS region is crucial for the recognition of the guanidine substrate. Replacement of Phe63 and Leu65 to Gly in the Stichopus enzyme caused a remarkable increase in the Kmarg. This indicates that Phe63 and Leu65 are associated with the arginine substrate-binding affinity. The hydrogen bond formed between the Asp62 and Arg193 residues is thought to play a key role in stabilizing the closed substrate-bound structure of AK. Mutants that eliminated this hydrogen bond had a considerably decreased Vmax, accompanied by a threefold increase in Kmarg. It is noted that the value of the Kmarg of the mutants became very close to the Kdarg value of the wild type. Six independent mutations were introduced in the GS region of Danio M-CK. Almost equivalent values of Kmcr and Kdcr in all of the mutants indicated that a typical synergism was completely lost. The results suggested that the Ile69 to Gly mutant, displaying a high Kmcr and a low Vmax, plays an important role in creatine-binding. This is consistent with the observation that in the structure of Torpedo CK, Ile69 provides a hydrophobic pocket to optimize creatine-binding.

Amino Acid Sequence↗