The 2.1 Å Structure of Torpedo californica Creatine Kinase Complexed with the ADP-Mg2+−NO3-−Creatine Transition-State Analogue Complex,

Lahiri, S. C.; Wang, Pan-Fen; Babbitt, Patricia C.; McLeish, Michael J.; Kenyon, George L.; Allen, Karen N.

doi:10.1021/bi026655p

Cited by 133 publications

(216 citation statements)

References 41 publications

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“…1). The GS region constitutes part of the flexible loop in the N-terminal domain of the crystal structures of Limulus AK and Torpedo CK [25,26]. There is a proportional relationship between the size of the deletion in the GS region and the mass of the phosphagen substrate.…”

Section: Structural Basis For Catalytic Properties Of Siphonosomamentioning

confidence: 99%

Hypotaurocyamine kinase evolved from a gene for arginine kinase

2005

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Hypotaurocyamine kinase (HTK) is a member of the highly conserved family of phosphagen kinases that includes creatine kinase (CK) and arginine kinase (AK). HTK is found only in sipunculid worms, and it shows activities for both the substrates hypotaurocyamine and taurocyamine. Determining how HTK evolved in sipunculids is particularly insightful because all sipunculid-allied animals have AK and only some sipunculids have HTK. We determined the cDNA sequence of HTK from the sipunculid worm Siphonosoma cumanense for the first time, cloned it in pMAL plasmid and expressed it in E. coli as a fusion protein with maltose-binding protein. The cDNAderived amino acid sequence of Siphonosoma HTK showed high amino acid identity with molluscan AKs. Nevertheless, the recombinant enzyme of Siphonosoma HTK showed no activity for the substrate arginine, but showed activity for taurocyamine. Comparison of the amino acid sequences of HTK and AK indicated that the amino acid residues necessary for the binding of the substrate arginine in AK have been completely lost in Siphonosoma HTK sequence. The phylogenetic analysis indicated that the HTK amino acid sequence was placed just outside the molluscan AK cluster, which formed a sister group with the arthropod and nematode AKs. These results suggest that Siphonosoma HTK evolved from a gene for molluscan AK. Moreover, to confirm this assertion, we determined by PCR that the gene for Siphonosoma HTK has a 5-exon/4-intron structure, which is homologous with that of the molluscan AK genes. Further, the positions of splice junctions were conserved exactly between the two genes. Thus, we conclude that Siphonosoma HTK has evolved from a primordial gene for molluscan AK.

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Section: Structural Basis For Catalytic Properties Of Siphonosomamentioning

confidence: 99%

Hypotaurocyamine kinase evolved from a gene for arginine kinase

2005

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“…In arginine kinase, interactions between Glu 312 and the guanidinium are prominent in this alignment. Creatine kinases have a valine at the corresponding position, which forms a hydrophobic mini-pocket accommodating the methyl group distinctive for creatine (16,17,21). However, mediation of specificity is more complex than lock-and-key.…”

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confidence: 99%

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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“…The three-dimensional structure of Sabellastarte AK2 was generated by SWISS-MODEL based on the TSAC structures of Limulus AK and Torpedo CK, both of which have a similar substrate-binding site [14,15]. Then we estimated the position of the substrate arginine in Sabellastarte AK2 by overlapping the position of L-arginine in the TSAC structure of Limulus AK (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2). While this residue does not appear to be directly involved in substrate binding in the TSAC structures of CK and AK, it is located close to the guanidine substrate-binding site [14,15]. Site-directed mutagenesis studies of this residue using rabbit CK and Einenia LK have shown that it has a significant effect on enzymatic activity and guanidino substrate specificity [20,21].…”

Section: Amino Acid 89mentioning

confidence: 99%

“…In the Torpedo CK TSAC structure, D320 forms a hydrogen bond with H66 on the N-terminal flexible loop and stabilizes the substrate-bound structure [14]. Moreover, in human muscle CK, it was reported that the disruption of the hydrogen bond (ion pair) between D320 and H66 caused a remarkable loss of activity (0.1% that of wild-type activity) [23].…”

Section: Amino Acid 320mentioning

confidence: 99%

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Identification of the key amino acid residues in Sabellastarte arginine kinase for distinguishing chiral guanidino substrates (d- and l-arginine)

Uda

Matumoto

Suzuki

2010

Journal of Molecular Catalysis B: Enzymatic

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Arginine kinase (AK, EC 2.7.3.3) is a phosphagen kinase widely distributed in lower and higher invertebrates. Sabellastarte indica AKs (AK1 and AK2) are the only AKs that use D-arginine in addition to L-arginine as a substrate. Sabellastarte indica AKs are therefore clearly unrelated to typical AK. The purpose of this work was to identify the amino acid residues responsible for distinguishing the chirality of D-and L-arginine. The three-dimensional structure of Sabellastarte AK2 was predicted using the SWISS-MODEL automated modeling server. Two amino acids, L64 in the N-terminal flexible loop and N320 in the C-terminal flexible loop, were found to be closest to the substrate arginine. We introduced several mutations around the predicted binding site of the substrate arginine. In the L64I mutant, the affinity for L-arginine was greatly increased (9.5-fold that of the wild-type), whereas its affinity for D-arginine was increased 2.9-fold, indicating that the L64I mutant enzyme was more specific for L-arginine. On the other hand, the L64V mutant showed a 1.7-fold decrease in affinity for L-arginine, but unchanged affinity for D-arginine. Thus the L64V mutant enzyme was more specific for D-arginine. Since the replacement of amino acid residue L64 by I or V significantly affected the affinity for L-arginine or D-arginine, it can be concluded that amino acid 64 is a key residue for distinguishing D-and L-arginine. Seven mutants at position 320 (N320H, Q, D, E, R, K and A) had considerably reduced enzymatic activity (0.05 to 52% of the wild-type). The reduction in enzyme activity was more significant when D-arginine was the substrate rather than L-arginine, except for N320D, suggesting that the carbonyl oxygen of the Asn320 side chain forms a hydrogen bond with the α-amino nitrogen attached to the asymmetric carbon of the D-arginine substrate. In addition, we found that even a residue remote from the guanidino substrate binding site, such as G54 and Y89 in Sabellastarte 3 AK2, significantly affected guanidino substrate specificity.4

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The 2.1 Å Structure of Torpedo californica Creatine Kinase Complexed with the ADP-Mg²⁺−NO₃^-−Creatine Transition-State Analogue Complex^,

Cited by 133 publications

References 41 publications

Hypotaurocyamine kinase evolved from a gene for arginine kinase

Hypotaurocyamine kinase evolved from a gene for arginine kinase

The Structure of Lombricine Kinase

Identification of the key amino acid residues in Sabellastarte arginine kinase for distinguishing chiral guanidino substrates (d- and l-arginine)

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