Adenylate kinase

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Adenylate kinase
Adenylate kinase 2C95.png
3D ribbon/surface model of adenylate kinase in complex with bis(adenosine)tetraphosphate (ADP-ADP)
Identifiers
SymbolADK
Pfam PF00406
InterPro IPR000850
PROSITE PDOC00104
SCOP2 1ake / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Adenylate kinase (EC 2.7.4.3) (also known as ADK or myokinase) is a phosphotransferase enzyme that catalyzes the interconversion of the various adenosine phosphates (ATP, ADP, and AMP). By constantly monitoring phosphate nucleotide levels inside the cell, ADK plays an important role in cellular energy homeostasis.

Contents

ADK_lid
PDB 1zip EBI.jpg
Bacillus stearothermophilus adenylate kinase
Identifiers
SymbolADK_lid
Pfam PF05191
InterPro IPR007862
PROSITE PDOC00104
SCOP2 1ake / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Adenylate kinase
Identifiers
EC no. 2.7.4.3
CAS no. 2598011
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Search
PMC articles
PubMed articles
NCBI proteins
PDB image 3HPQ showing the ADK enzyme skeleton in cartoon and the key residues as sticks and labeled according to their placement in E. coli, crystallized with Ap5A inhibitor. Pymol file v2.png
PDB image 3HPQ showing the ADK enzyme skeleton in cartoon and the key residues as sticks and labeled according to their placement in E. coli, crystallized with Ap5A inhibitor.

Substrate and products

The reaction catalyzed is:

ATP + AMP ⇔ 2 ADP

The equilibrium constant varies with condition, but it is close to 1. [1] Thus, ΔGo for this reaction is close to zero. In muscle from a variety of species of vertebrates and invertebrates, the concentration of ATP is typically 7-10 times that of ADP, and usually greater than 100 times that of AMP. [2] The rate of oxidative phosphorylation is controlled by the availability of ADP. Thus, the mitochondrion attempts to keep ATP levels high due to the combined action of adenylate kinase and the controls on oxidative phosphorylation.

Isozymes

To date there have been nine human ADK protein isoforms identified. While some of these are ubiquitous throughout the body, some are localized into specific tissues. For example, ADK7 and ADK8 are both only found in the cytosol of cells; and ADK7 is found in skeletal muscle whereas ADK8 is not. [3] Not only do the locations of the various isoforms within the cell vary, but the binding of substrate to the enzyme and kinetics of the phosphoryl transfer are different as well. ADK1, the most abundant cytosolic ADK isozyme, has a Km about a thousand times higher than the Km of ADK7 and 8, indicating a much weaker binding of ADK1 to AMP. [4] Sub-cellular localization of the ADK enzymes is done by including a targeting sequence in the protein. [3] Each isoform also has different preference for NTP's. Some will only use ATP, whereas others will accept GTP, UTP, and CTP as the phosphoryl carrier.

Some of these isoforms prefer other NTP's entirely. There is a mitochondrial GTP:AMP phosphotransferase, also specific for the phosphorylation of AMP, that can only use GTP or ITP as the phosphoryl donor. [5] ADK has also been identified in different bacterial species and in yeast. [6] Two further enzymes are known to be related to the ADK family, i.e. yeast uridine monophosphokinase and slime mold UMP-CMP kinase. Some residues are conserved across these isoforms, indicating how essential they are for catalysis. One of the most conserved areas includes an Arg residue, whose modification inactivates the enzyme, together with an Asp that resides in the catalytic cleft of the enzyme and participates in a salt bridge.

Subfamilies

Mechanism

Phosphoryl transfer only occurs on closing of the 'open lid'. This causes an exclusion of water molecules that brings the substrates in proximity to each other, [7] lowering the energy barrier for the nucleophilic attack by the α-phosphoryl of AMP on the γ-phosphoryl group of ATP resulting in formation of ADP by transfer of the γ-phosphoryl group to AMP. In the crystal structure of the ADK enzyme from E. coli with inhibitor Ap5A, the Arg88 residue binds the Ap5A at the α-phosphate group. It has been shown that the mutation R88G results in 99% loss of catalytic activity of this enzyme, suggesting that this residue is intimately involved in the phosphoryl transfer. [8] Another highly conserved residue is Arg119, which lies in the adenosine binding region of the ADK, and acts to sandwich the adenine in the active site. It has been suggested that the promiscuity of these enzymes in accepting other NTP's is due to this relatively inconsequential interactions of the base in the ATP binding pocket. [9] A network of positive, conserved residues (Lys13, Arg123, Arg156, and Arg167 in ADK from E. coli) stabilize the buildup of negative charge on phosphoryl group during the transfer. Two distal aspartate residues bind to the arginine network, causing the enzyme to fold and reduces its flexibility. A magnesium cofactor is also required, essential for increasing the electrophilicity of the phosphate on AMP, though this magnesium ion is only held in the active pocket by electrostatic interactions and dissociates easily. [9]

Structure

Residues of ADKE. coli involved in substrate binding Binding of Ap5A in the active site of Adenylate Kinase with the Arginine network labeled.png
Residues of ADKE. coli involved in substrate binding

Flexibility and plasticity allow proteins to bind to ligands, form oligomers, aggregate, and perform mechanical work. [10] Large conformational changes in proteins play an important role in cellular signaling. Adenylate Kinase is a signal transducing protein; thus, the balance between conformations regulates protein activity. ADK has a locally unfolded state that becomes depopulated upon binding. [11]

Describes the generic kinetic cycle of the ADK enzyme family. Ternary complex is labeled. Kinetic cycle of adenylate kinase.png
Describes the generic kinetic cycle of the ADK enzyme family. Ternary complex is labeled.

A 2007 study by Whitford et al. shows the conformations of ADK when binding with ATP or AMP. [10] The study shows that there are three relevant conformations or structures of ADK—CORE, Open, and Closed. In ADK, there are two small domains called the LID and NMP. [12] ATP binds in the pocket formed by the LID and CORE domains. AMP binds in the pocket formed by the NMP and CORE domains. The Whitford study also reported findings that show that localized regions of a protein unfold during conformational transitions. This mechanism reduces the strain and enhances catalytic efficiency. Local unfolding is the result of competing strain energies in the protein. [10]

The local (thermodynamic) stability of the substrate-binding domains ATPlid and AMPlid has been shown to be significantly lower when compared with the CORE domain in ADKE. coli. [13] Furthermore, it has been shown that the two subdomains (ATPlid and AMPlid) can fold and unfold in a "non-cooperative manner." [13] Binding of the substrates causes preference for 'closed' conformations amongst those that are sampled by ADK. These 'closed' conformations are hypothesized to help with removal of water from the active site to avoid wasteful hydrolysis of ATP in addition to helping optimize alignment of substrates for phosphoryl-transfer. [14] Furthermore, it has been shown that the apoenzyme will still sample the 'closed' conformations of the ATPlid and AMPlid domains in the absence of substrates. [7] When comparing the rate of opening of the enzyme (which allows for product release) and the rate of closing that accompanies substrate binding, closing was found to be the slower process.

Function

Metabolic monitoring

The ability for a cell to dynamically measure energetic levels provides it with a method to monitor metabolic processes. [15] By continually monitoring and altering the levels of ATP and the other adenyl phosphates (ADP and AMP levels) adenylate kinase is an important regulator of energy expenditure at the cellular level. [16] As energy levels change under different metabolic stresses adenylate kinase is then able to generate AMP; which itself acts as a signaling molecule in further signaling cascades. This generated AMP can, for example, stimulate various AMP-dependent receptors such as those involved in glycolytic pathways, K-ATP channels, and 5' AMP-activated protein kinase (AMPK). [15] Common factors that influence adenine nucleotide levels, and therefore ADK activity are exercise, stress, changes in hormone levels, and diet. [15] It facilitates decoding of cellular information by catalyzing nucleotide exchange in the intimate “sensing zone” of metabolic sensors. [15]

ADK shuttle

Adenylate kinase is present in mitochondrial and myofibrillar compartments in the cell, and it makes two high-energy phosphoryls (β and γ) of ATP available to be transferred between adenine nucleotide molecules. [15] [16] In essence, adenylate kinase shuttles ATP to sites of high energy consumption and removes the AMP generated over the course of those reactions. These sequential phosphotransfer relays ultimately result in propagation of the phosphoryl groups along collections of ADK molecules. [15] This process can be thought of as a bucket brigade of ADK molecules that results in changes in local intracellular metabolic flux without apparent global changes in metabolite concentrations. [15] This process is extremely important for overall homeostasis of the cell. [15]

Disease relevance

Nucleoside diphosphate kinase deficiency

Nucleoside diphosphate (NDP) kinase catalyzes in vivo ATP-dependent synthesis of ribo- and deoxyribonucleoside triphosphates. In mutated Escherichia coli that had a disrupted nucleoside diphosphate kinase, adenylate kinase performed dual enzymatic functions. ADK complements nucleoside diphosphate kinase deficiency. [17]

AK1 and post-ischemic coronary reflow

Knock out of AK1 disrupts the synchrony between inorganic phosphate and turnover at ATP-consuming sites and ATP synthesis sites. This reduces the energetic signal communication in the post-ischemic heart and precipitates inadequate coronary reflow following ischemia-reperfusion. [18]

ADK2 deficiency

Adenylate Kinase 2 (AK2) deficiency in humans causes hematopoietic defects associated with sensorineural deafness. [19] Reticular dysgenesis is an autosomal recessive form of human combined immunodeficiency. It is also characterized by an impaired lymphoid maturation and early differentiation arrest in the myeloid lineage. AK2 deficiency results in absent or a large decrease in the expression of proteins. AK2 is specifically expressed in the stria vascularis of the inner ear which indicates why individuals with an AK2 deficiency will have sensorineural deafness. [19]

Structural adaptations

AK1 genetic ablation decreases tolerance to metabolic stress. AK1 deficiency induces fiber-type specific variation in groups of transcripts in glycolysis and mitochondrial metabolism. [20] This supports muscle energy metabolism.

Plastidial ADK deficiency in Arabidopsis thaliana

Enhanced growth and elevated photosynthetic amino acid is associated with plastidial adenylate kinase deficiency in Arabidopsis thaliana . [21]

Related Research Articles

<span class="mw-page-title-main">Adenosine triphosphate</span> Energy-carrying molecule in living cells

Adenosine triphosphate (ATP) is a nucleotide that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP). Other processes regenerate ATP. It is also a precursor to DNA and RNA, and is used as a coenzyme. A human adult processes around 50 kg of ATP daily.

<span class="mw-page-title-main">Adenylyl cyclase</span> Enzyme with key regulatory roles in most cells

Adenylate cyclase is an enzyme with systematic name ATP diphosphate-lyase . It catalyzes the following reaction:

<span class="mw-page-title-main">Kinase</span> Enzyme catalyzing transfer of phosphate groups onto specific substrates

In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group. These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis.

<span class="mw-page-title-main">Adenosine monophosphate</span> Chemical compound

Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine. It is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-.

<span class="mw-page-title-main">Phosphofructokinase 1</span> Class of enzymes

Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory steps of glycolysis. PFK is able to regulate glycolysis through allosteric inhibition, and in this way, the cell can increase or decrease the rate of glycolysis in response to the cell's energy requirements. For example, a high ratio of ATP to ADP will inhibit PFK and glycolysis. The key difference between the regulation of PFK in eukaryotes and prokaryotes is that in eukaryotes PFK is activated by fructose 2,6-bisphosphate. The purpose of fructose 2,6-bisphosphate is to supersede ATP inhibition, thus allowing eukaryotes to have greater sensitivity to regulation by hormones like glucagon and insulin.

<span class="mw-page-title-main">Pyruvate kinase</span> Class of enzymes

Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.

<span class="mw-page-title-main">Phosphoglucomutase</span>

Phosphoglucomutase is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction.

The adenylate energy charge is an index used to measure the energy status of biological cells.

<span class="mw-page-title-main">Glycogen phosphorylase</span> Class of enzymes

Glycogen phosphorylase is one of the phosphorylase enzymes. Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects.

<span class="mw-page-title-main">Succinyl coenzyme A synthetase</span>

Succinyl coenzyme A synthetase is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate. The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule from an inorganic phosphate molecule and a nucleoside diphosphate molecule. It plays a key role as one of the catalysts involved in the citric acid cycle, a central pathway in cellular metabolism, and it is located within the mitochondrial matrix of a cell.

<span class="mw-page-title-main">Phosphofructokinase</span> Enzyme in glycolysis

Phosphofructokinase (PFK) is a kinase enzyme that phosphorylates fructose 6-phosphate in glycolysis.

Pantothenate kinase (EC 2.7.1.33, PanK; CoaA) is the first enzyme in the Coenzyme A (CoA) biosynthetic pathway. It phosphorylates pantothenate (vitamin B5) to form 4'-phosphopantothenate at the expense of a molecule of adenosine triphosphate (ATP). It is the rate-limiting step in the biosynthesis of CoA.

<span class="mw-page-title-main">Deoxycytidine kinase</span> Protein-coding gene in the species Homo sapiens

Deoxycytidine kinase (dCK) is an enzyme which is encoded by the DCK gene in humans. dCK predominantly phosphorylates deoxycytidine (dC) and converts dC into deoxycytidine monophosphate. dCK catalyzes one of the initial steps in the nucleoside salvage pathway and has the potential to phosphorylate other preformed nucleosides, specifically deoxyadenosine (dA) and deoxyguanosine (dG), and convert them into their monophosphate forms. There has been recent biomedical research interest in investigating dCK's potential as a therapeutic target for different types of cancer.

<span class="mw-page-title-main">Ribose-phosphate diphosphokinase</span> Class of enzymes

Ribose-phosphate diphosphokinase is an enzyme that converts ribose 5-phosphate into phosphoribosyl pyrophosphate (PRPP). It is classified under EC 2.7.6.1.

<span class="mw-page-title-main">ADP-ribose diphosphatase</span>

ADP-ribose diphosphatase (EC 3.6.1.13) is an enzyme that catalyzes a hydrolysis reaction in which water nucleophilically attacks ADP-ribose to produce AMP and D-ribose 5-phosphate. Enzyme hydrolysis occurs by the breakage of a phosphoanhydride bond and is dependent on Mg2+ ions that are held in complex by the enzyme.

<span class="mw-page-title-main">Histidine kinase</span>

Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homodimers that exhibit autokinase, phosphotransfer, and phosphatase activity. HKs can act as cellular receptors for signaling molecules in a way analogous to tyrosine kinase receptors (RTK). Multifunctional receptor molecules such as HKs and RTKs typically have portions on the outside of the cell that bind to hormone- or growth factor-like molecules, portions that span the cell membrane, and portions within the cell that contain the enzymatic activity. In addition to kinase activity, the intracellular domains typically have regions that bind to a secondary effector molecule or complex of molecules that further propagate signal transduction within the cell. Distinct from other classes of protein kinases, HKs are usually parts of a two-component signal transduction mechanisms in which HK transfers a phosphate group from ATP to a histidine residue within the kinase, and then to an aspartate residue on the receiver domain of a response regulator protein. More recently, the widespread existence of protein histidine phosphorylation distinct from that of two-component histidine kinases has been recognised in human cells. In marked contrast to Ser, Thr and Tyr phosphorylation, the analysis of phosphorylated Histidine using standard biochemical and mass spectrometric approaches is much more challenging, and special procedures and separation techniques are required for their preservation alongside classical Ser, Thr and Tyr phosphorylation on proteins isolated from human cells.

In enzymology, a nucleoside-phosphate kinase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribulokinase</span>

Phosphoribulokinase (PRK) (EC 2.7.1.19) is an essential photosynthetic enzyme that catalyzes the ATP-dependent phosphorylation of ribulose 5-phosphate (RuP) into ribulose 1,5-bisphosphate (RuBP), both intermediates in the Calvin Cycle. Its main function is to regenerate RuBP, which is the initial substrate and CO2-acceptor molecule of the Calvin Cycle. PRK belongs to the family of transferase enzymes, specifically those transferring phosphorus-containing groups (phosphotransferases) to an alcohol group acceptor. Along with ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCo), phosphoribulokinase is unique to the Calvin Cycle. Therefore, PRK activity often determines the metabolic rate in organisms for which carbon fixation is key to survival. Much initial work on PRK was done with spinach leaf extracts in the 1950s; subsequent studies of PRK in other photosynthetic prokaryotic and eukaryotic organisms have followed. The possibility that PRK might exist was first recognized by Weissbach et al. in 1954; for example, the group noted that carbon dioxide fixation in crude spinach extracts was enhanced by the addition of ATP. The first purification of PRK was conducted by Hurwitz and colleagues in 1956.

ATP + Mg2+ - D-ribulose 5-phosphate  ADP + D-ribulose 1,5-bisphosphate
<span class="mw-page-title-main">Riboflavin kinase</span>

In enzymology, a riboflavin kinase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Purine nucleotide cycle</span>

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle.

References

  1. ↑ The NIST Thermodynamics of Enzyme-Catalyzed Reactions database, http://xpdb.nist.gov/enzyme_thermodynamics/enzyme1.pl Archived 2016-11-09 at the Wayback Machine , Goldberg RN, Tewari YB, Bhat TN (November 2004). "Thermodynamics of enzyme-catalyzed reactions--a database for quantitative biochemistry". Bioinformatics. 20 (16): 2874–7. doi: 10.1093/bioinformatics/bth314 . PMID   15145806., gives equilibrium constants, search for adenylate kinase under enzymes
  2. ↑ Beis I, Newsholme EA (October 1975). "The contents of adenine nucleotides, phosphagens and some glycolytic intermediates in resting muscles from vertebrates and invertebrates". The Biochemical Journal. 152 (1): 23–32. doi:10.1042/bj1520023. PMC   1172435 . PMID   1212224.
  3. 1 2 Panayiotou C, Solaroli N, Karlsson A (April 2014). "The many isoforms of human adenylate kinases". The International Journal of Biochemistry & Cell Biology. 49: 75–83. doi:10.1016/j.biocel.2014.01.014. PMID   24495878.
  4. ↑ Panayiotou C, Solaroli N, Xu Y, Johansson M, Karlsson A (February 2011). "The characterization of human adenylate kinases 7 and 8 demonstrates differences in kinetic parameters and structural organization among the family of adenylate kinase isoenzymes" (PDF). The Biochemical Journal. 433 (3): 527–34. doi:10.1042/BJ20101443. PMID   21080915. S2CID   33249169.
  5. ↑ Tomasselli AG, Noda LH (January 1979). "Mitochondrial GTP-AMP phosphotransferase. 2. Kinetic and equilibrium dialysis studies". European Journal of Biochemistry. 93 (2): 263–7. doi: 10.1111/j.1432-1033.1979.tb12819.x . PMID   218813.
  6. ↑ Cooper AJ, Friedberg EC (May 1992). "A putative second adenylate kinase-encoding gene from the yeast Saccharomyces cerevisiae". Gene. 114 (1): 145–8. doi:10.1016/0378-1119(92)90721-Z. PMID   1587477.
  7. 1 2 Henzler-Wildman KA, Thai V, Lei M, Ott M, Wolf-Watz M, Fenn T, Pozharski E, Wilson MA, Petsko GA, Karplus M, Hübner CG, Kern D (December 2007). "Intrinsic motions along an enzymatic reaction trajectory". Nature. 450 (7171): 838–44. Bibcode:2007Natur.450..838H. doi:10.1038/nature06410. PMID   18026086. S2CID   4406037.
  8. ↑ Reinstein J, Gilles AM, Rose T, Wittinghofer A, Saint Girons I, Bârzu O, Surewicz WK, Mantsch HH (May 1989). "Structural and catalytic role of arginine 88 in Escherichia coli adenylate kinase as evidenced by chemical modification and site-directed mutagenesis". The Journal of Biological Chemistry. 264 (14): 8107–12. doi: 10.1016/S0021-9258(18)83156-8 . PMID   2542263.
  9. 1 2 Müller CW, Schulz GE (March 1992). "Structure of the complex between adenylate kinase from Escherichia coli and the inhibitor Ap5A refined at 1.9 A resolution. A model for a catalytic transition state". Journal of Molecular Biology. 224 (1): 159–77. doi:10.2210/pdb1ake/pdb. PMID   1548697.
  10. 1 2 3 Whitford PC, Miyashita O, Levy Y, Onuchic JN (March 2007). "Conformational transitions of adenylate kinase: switching by cracking". Journal of Molecular Biology. 366 (5): 1661–71. doi:10.1016/j.jmb.2006.11.085. PMC   2561047 . PMID   17217965.
  11. ↑ Schrank TP, Bolen DW, Hilser VJ (October 2009). "Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins". Proceedings of the National Academy of Sciences of the United States of America. 106 (40): 16984–9. Bibcode:2009PNAS..10616984S. doi: 10.1073/pnas.0906510106 . PMC   2761315 . PMID   19805185.
  12. ↑ Daily MD, Phillips GN, Cui Q (July 2010). "Many local motions cooperate to produce the adenylate kinase conformational transition". Journal of Molecular Biology. 400 (3): 618–31. doi:10.1016/j.jmb.2010.05.015. PMC   2902635 . PMID   20471396.
  13. 1 2 Rundqvist L, Adén J, Sparrman T, Wallgren M, Olsson U, Wolf-Watz M (March 2009). "Noncooperative folding of subdomains in adenylate kinase". Biochemistry. 48 (9): 1911–27. doi:10.1021/bi8018042. PMID   19219996.
  14. ↑ Olsson U, Wolf-Watz M (November 2010). "Overlap between folding and functional energy landscapes for adenylate kinase conformational change". Nature Communications. 1 (8): 111. Bibcode:2010NatCo...1..111O. doi: 10.1038/ncomms1106 . PMID   21081909.
  15. 1 2 3 4 5 6 7 8 Dzeja P, Terzic A (April 2009). "Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing". International Journal of Molecular Sciences. 10 (4): 1729–72. doi: 10.3390/ijms10041729 . PMC   2680645 . PMID   19468337.
  16. 1 2 Dzeja PP, Chung S, Faustino RS, Behfar A, Terzic A (April 2011). "Developmental enhancement of adenylate kinase-AMPK metabolic signaling axis supports stem cell cardiac differentiation". PLOS ONE. 6 (4): e19300. Bibcode:2011PLoSO...619300D. doi: 10.1371/journal.pone.0019300 . PMC   3083437 . PMID   21556322.
  17. ↑ Lu Q, Inouye M (June 1996). "Adenylate kinase complements nucleoside diphosphate kinase deficiency in nucleotide metabolism". Proceedings of the National Academy of Sciences of the United States of America. 93 (12): 5720–5. Bibcode:1996PNAS...93.5720L. doi: 10.1073/pnas.93.12.5720 . PMC   39127 . PMID   8650159.
  18. ↑ Dzeja PP, Bast P, Pucar D, Wieringa B, Terzic A (October 2007). "Defective metabolic signaling in adenylate kinase AK1 gene knock-out hearts compromises post-ischemic coronary reflow". The Journal of Biological Chemistry. 282 (43): 31366–72. doi: 10.1074/jbc.M705268200 . PMC   3232003 . PMID   17704060.
  19. 1 2 Lagresle-Peyrou C, Six EM, Picard C, Rieux-Laucat F, Michel V, Ditadi A, Demerens-de Chappedelaine C, Morillon E, Valensi F, Simon-Stoos KL, Mullikin JC, Noroski LM, Besse C, Wulffraat NM, Ferster A, Abecasis MM, Calvo F, Petit C, Candotti F, Abel L, Fischer A, Cavazzana-Calvo M (January 2009). "Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness". Nature Genetics. 41 (1): 106–11. doi:10.1038/ng.278. PMC   2612090 . PMID   19043416.
  20. ↑ Janssen E, de Groof A, Wijers M, Fransen J, Dzeja PP, Terzic A, Wieringa B (April 2003). "Adenylate kinase 1 deficiency induces molecular and structural adaptations to support muscle energy metabolism". The Journal of Biological Chemistry. 278 (15): 12937–45. doi: 10.1074/jbc.M211465200 . hdl: 2066/186091 . PMID   12562761.
  21. ↑ Carrari F, Coll-Garcia D, Schauer N, Lytovchenko A, Palacios-Rojas N, Balbo I, Rosso M, Fernie AR (January 2005). "Deficiency of a plastidial adenylate kinase in Arabidopsis results in elevated photosynthetic amino acid biosynthesis and enhanced growth". Plant Physiology. 137 (1): 70–82. doi:10.1104/pp.104.056143. PMC   548839 . PMID   15618410.
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