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PDBsum entry 1bx4

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protein ligands metals links
Transferase PDB id
1bx4
Jmol
Contents
Protein chain
342 a.a. *
Ligands
ADN ×2
Metals
_CL ×2
_MG ×3
Waters ×354
* Residue conservation analysis
PDB id:
1bx4
Name: Transferase
Title: Structure of human adenosine kinase at 1.50 angstroms
Structure: Protein (adenosine kinase). Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: native protein was expressed in bl21[de3] cells seleno methionine protein in b834[de3] cells
Resolution:
1.50Å     R-factor:   0.192     R-free:   0.226
Authors: I.I.Mathews,M.D.Erion,S.E.Ealick
Key ref:
I.I.Mathews et al. (1998). Structure of human adenosine kinase at 1.5 A resolution. Biochemistry, 37, 15607-15620. PubMed id: 9843365 DOI: 10.1021/bi9815445
Date:
13-Oct-98     Release date:   13-Oct-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P55263  (ADK_HUMAN) -  Adenosine kinase
Seq:
Struc:
362 a.a.
342 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     AMP salvage   14 terms 
  Biochemical function     nucleotide binding     8 terms  

 

 
DOI no: 10.1021/bi9815445 Biochemistry 37:15607-15620 (1998)
PubMed id: 9843365  
 
 
Structure of human adenosine kinase at 1.5 A resolution.
I.I.Mathews, M.D.Erion, S.E.Ealick.
 
  ABSTRACT  
 
Adenosine kinase (AK) is a key enzyme in the regulation of extracellular adenosine and intracellular adenylate levels. Inhibitors of adenosine kinase elevate adenosine to levels that activate nearby adenosine receptors and produce a wide variety of therapeutically beneficial activities. Accordingly, AK is a promising target for new analgesic, neuroprotective, and cardioprotective agents. We determined the structure of human adenosine kinase by X-ray crystallography using MAD phasing techniques and refined the structure to 1.5 A resolution. The enzyme structure consisted of one large alpha/beta domain with nine beta-strands, eight alpha-helices, and one small alpha/beta-domain with five beta-strands and two alpha-helices. The active site is formed along the edge of the beta-sheet in the large domain while the small domain acts as a lid to cover the upper face of the active site. The overall structure is similar to the recently reported structure of ribokinase from Escherichia coli [Sigrell et al. (1998) Structure 6, 183-193]. The structure of ribokinase was determined at 1.8 A resolution and represents the first structure of a new family of carbohydrate kinases. Two molecules of adenosine were present in the AK crystal structure with one adenosine molecule located in a site that matches the ribose site in ribokinase and probably represents the substrate-binding site. The second adenosine site overlaps the ADP site in ribokinase and probably represents the ATP site. A Mg2+ ion binding site is observed in a trough between the two adenosine sites. The structure of the active site is consistent with the observed substrate specificity. The active-site model suggests that Asp300 is an important catalytic residue involved in the deprotonation of the 5'-hydroxyl during the phosphate transfer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20693694 H.Xu (2010).
Enhancing MAD F(A) data for substructure determination.
  Acta Crystallogr D Biol Crystallogr, 66, 945-949.  
20686683 R.Potestio, C.Micheletti, and H.Orland (2010).
Knotted vs. unknotted proteins: evidence of knot-promoting loops.
  PLoS Comput Biol, 6, e1000864.  
20881134 S.Palchykova, R.Winsky-Sommerer, H.Y.Shen, D.Boison, A.Gerling, and I.Tobler (2010).
Manipulation of adenosine kinase affects sleep regulation in mice.
  J Neurosci, 30, 13157-13165.  
19237742 C.H.Trinh, A.Asipu, D.T.Bonthron, and S.E.Phillips (2009).
Structures of alternatively spliced isoforms of human ketohexokinase.
  Acta Crystallogr D Biol Crystallogr, 65, 201-211.
PDB codes: 2hqq 2hw1
19348578 C.T.Jurgenson, T.P.Begley, and S.E.Ealick (2009).
The structural and biochemical foundations of thiamin biosynthesis.
  Annu Rev Biochem, 78, 569-603.  
19049516 D.Vannoni, R.Leoncini, S.Giglioni, N.Niccolai, O.Spiga, E.Aceto, and E.Marinello (2009).
Evidence of a new phosphoryl transfer system in nucleotide metabolism.
  FEBS J, 276, 271-285.  
19548321 V.Guixé, and F.Merino (2009).
The ADP-dependent sugar kinase family: kinetic and evolutionary aspects.
  IUBMB Life, 61, 753-761.  
19021762 H.Ota, S.Sakasegawa, Y.Yasuda, S.Imamura, and T.Tamura (2008).
A novel nucleoside kinase from Burkholderia thailandensis.
  FEBS J, 275, 5865-5872.  
18219117 H.Xu, and C.M.Weeks (2008).
Rapid and automated substructure solution by Shake-and-Bake.
  Acta Crystallogr D Biol Crystallogr, 64, 172-177.  
18004772 I.I.Mathews, D.McMullan, M.D.Miller, J.M.Canaves, M.A.Elsliger, R.Floyd, S.K.Grzechnik, L.Jaroszewski, H.E.Klock, E.Koesema, J.S.Kovarik, A.Kreusch, P.Kuhn, T.M.McPhillips, A.T.Morse, K.Quijano, C.L.Rife, R.Schwarzenbacher, G.Spraggon, R.C.Stevens, H.van den Bedem, D.Weekes, G.Wolf, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2008).
Crystal structure of 2-keto-3-deoxygluconate kinase (TM0067) from Thermotoga maritima at 2.05 A resolution.
  Proteins, 70, 603-608.
PDB code: 2afb
17384969 E.Dyguda-Kazimierowicz, W.A.Sokalski, and J.LeszczyƄski (2007).
Non-empirical study of the phosphorylation reaction catalyzed by 4-methyl-5-beta-hydroxyethylthiazole kinase: relevance of the theory of intermolecular interactions.
  J Mol Model, 13, 839-849.  
17766369 F.N.Musayev, M.L.di Salvo, T.P.Ko, A.K.Gandhi, A.Goswami, V.Schirch, and M.K.Safo (2007).
Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation.
  Protein Sci, 16, 2184-2194.
PDB codes: 2yxt 2yxu
17597075 M.C.Reddy, S.K.Palaninathan, N.D.Shetty, J.L.Owen, M.D.Watson, and J.C.Sacchettini (2007).
High resolution crystal structures of Mycobacterium tuberculosis adenosine kinase: insights into the mechanism and specificity of this novel prokaryotic enzyme.
  J Biol Chem, 282, 27334-27342.
PDB codes: 2pkf 2pkk 2pkm 2pkn
17763527 R.M.Marin, K.G.Franchini, and S.A.Rocco (2007).
Analysis of adenosine by RP-HPLC method and its application to the study of adenosine kinase kinetics.
  J Sep Sci, 30, 2473-2479.  
17021658 T.Hansen, L.Arnfors, R.Ladenstein, and P.Schönheit (2007).
The phosphofructokinase-B (MJ0406) from Methanocaldococcus jannaschii represents a nucleoside kinase with a broad substrate specificity.
  Extremophiles, 11, 105-114.  
17306769 Y.A.Kim, A.Sharon, C.K.Chu, R.H.Rais, O.N.Al Safarjalani, F.N.Naguib, and M.H.el Kouni (2007).
Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents.
  Biochem Pharmacol, 73, 1558-1572.  
17242506 Y.Zhang, M.H.El Kouni, and S.E.Ealick (2007).
Substrate analogs induce an intermediate conformational change in Toxoplasma gondii adenosine kinase.
  Acta Crystallogr D Biol Crystallogr, 63, 126-134.
PDB codes: 2a9y 2a9z 2aa0 2ab8
16497163 C.Wrenger, M.L.Eschbach, I.B.Müller, N.P.Laun, T.P.Begley, and R.D.Walter (2006).
Vitamin B1 de novo synthesis in the human malaria parasite Plasmodium falciparum depends on external provision of 4-amino-5-hydroxymethyl-2-methylpyrimidine.
  Biol Chem, 387, 41-51.  
16444581 J.Park, B.Singh, and R.S.Gupta (2006).
Inhibition of adenosine kinase by phosphonate and bisphosphonate derivatives.
  Mol Cell Biochem, 283, 11-21.  
16737961 J.S.Lott, B.Paget, J.M.Johnston, L.T.Delbaere, J.A.Sigrell-Simon, M.J.Banfield, and E.N.Baker (2006).
The structure of an ancient conserved domain establishes a structural basis for stable histidine phosphorylation and identifies a new family of adenosine-specific kinases.
  J Biol Chem, 281, 22131-22141.
PDB codes: 1wvq 2gl0
16929110 L.Arnfors, T.Hansen, P.Schönheit, R.Ladenstein, and W.Meining (2006).
Structure of Methanocaldococcus jannaschii nucleoside kinase: an archaeal member of the ribokinase family.
  Acta Crystallogr D Biol Crystallogr, 62, 1085-1097.
PDB codes: 2c49 2c4e
16740960 M.K.Safo, F.N.Musayev, M.L.di Salvo, S.Hunt, J.B.Claude, and V.Schirch (2006).
Crystal structure of pyridoxal kinase from the Escherichia coli pdxK gene: implications for the classification of pyridoxal kinases.
  J Bacteriol, 188, 4542-4552.
PDB codes: 2ddm 2ddo 2ddw
16421444 Y.Zhang, M.H.El Kouni, and S.E.Ealick (2006).
Structure of Toxoplasma gondii adenosine kinase in complex with an ATP analog at 1.1 angstroms resolution.
  Acta Crystallogr D Biol Crystallogr, 62, 140-145.
PDB code: 2abs
15590634 C.Wrenger, M.L.Eschbach, I.B.Müller, D.Warnecke, and R.D.Walter (2005).
Analysis of the vitamin B6 biosynthesis pathway in the human malaria parasite Plasmodium falciparum.
  J Biol Chem, 280, 5242-5248.  
15983421 H.Xu, C.M.Weeks, and H.A.Hauptman (2005).
Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
  Acta Crystallogr D Biol Crystallogr, 61, 976-981.  
  16511104 L.Arnfors, T.Hansen, W.Meining, P.Schönheit, and R.Ladenstein (2005).
Expression, purification, crystallization and preliminary X-ray analysis of a nucleoside kinase from the hyperthermophile Methanocaldococcus jannaschii.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 591-594.  
15735337 T.C.Appleby, G.Larson, I.W.Cheney, H.Walker, J.Z.Wu, W.Zhong, Z.Hong, and N.Yao (2005).
Structure of human uridine-cytidine kinase 2 determined by SIRAS using a rotating-anode X-ray generator and a single samarium derivative.
  Acta Crystallogr D Biol Crystallogr, 61, 278-284.
PDB code: 1xrj
  16511094 Y.Wang, M.C.Long, S.Ranganathan, V.Escuyer, W.B.Parker, and R.Li (2005).
Overexpression, purification and crystallographic analysis of a unique adenosine kinase from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 553-557.  
15317590 B.Sahin, J.W.Kansy, A.C.Nairn, J.Spychala, S.E.Ealick, A.A.Fienberg, R.W.Greene, and J.A.Bibb (2004).
Molecular characterization of recombinant mouse adenosine kinase and evaluation as a target for protein phosphorylation.
  Eur J Biochem, 271, 3547-3555.  
15140885 K.Chaudhary, J.A.Darling, L.M.Fohl, W.J.Sullivan, R.G.Donald, E.R.Pfefferkorn, B.Ullman, and D.S.Roos (2004).
Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii.
  J Biol Chem, 279, 31221-31227.  
15281129 K.Manikandan, and S.Ramakumar (2004).
The occurrence of C--H...O hydrogen bonds in alpha-helices and helix termini in globular proteins.
  Proteins, 56, 768-781.  
14722069 M.H.Li, F.Kwok, W.R.Chang, S.Q.Liu, S.C.Lo, J.P.Zhang, T.Jiang, and D.C.Liang (2004).
Conformational changes in the reaction of pyridoxal kinase.
  J Biol Chem, 279, 17459-17465.
PDB codes: 1rft 1rfu 1rfv
15229886 N.Fernandez-Fuentes, A.Hermoso, J.Espadaler, E.Querol, F.X.Aviles, and B.Oliva (2004).
Classification of common functional loops of kinase super-families.
  Proteins, 56, 539-555.  
14609716 A.R.Van Rompay, M.Johansson, and A.Karlsson (2003).
Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases.
  Pharmacol Ther, 100, 119-139.  
14594827 M.C.Long, V.Escuyer, and W.B.Parker (2003).
Identification and characterization of a unique adenosine kinase from Mycobacterium tuberculosis.
  J Bacteriol, 185, 6548-6555.  
12527754 R.Cabrera, H.Fischer, S.Trapani, A.F.Craievich, R.C.Garratt, V.Guixé, and J.Babul (2003).
Domain motions and quaternary packing of phosphofructokinase-2 from Escherichia coli studied by small angle x-ray scattering and homology modeling.
  J Biol Chem, 278, 12913-12919.  
12670309 Y.Lu, H.J.Chung, Y.Li, and P.A.Rosenberg (2003).
NMDA receptor-mediated extracellular adenosine accumulation in rat forebrain neurons in culture is associated with inhibition of adenosine kinase.
  Eur J Neurosci, 17, 1213-1222.  
12244046 A.Chakraborty, I.Das, R.Datta, B.Sen, D.Bhattacharyya, C.Mandal, and A.K.Datta (2002).
A single-domain cyclophilin from Leishmania donovani reactivates soluble aggregates of adenosine kinase by isomerase-independent chaperone function.
  J Biol Chem, 277, 47451-47460.  
11997462 D.Boison, L.Scheurer, V.Zumsteg, T.Rülicke, P.Litynski, B.Fowler, S.Brandner, and H.Mohler (2002).
Neonatal hepatic steatosis by disruption of the adenosine kinase gene.
  Proc Natl Acad Sci U S A, 99, 6985-6990.  
12237466 H.Tsuge, H.Sakuraba, T.Kobe, A.Kujime, N.Katunuma, and T.Ohshima (2002).
Crystal structure of the ADP-dependent glucokinase from Pyrococcus horikoshii at 2.0-A resolution: a large conformational change in ADP-dependent glucokinase.
  Protein Sci, 11, 2456-2463.
PDB code: 1l2l
11900549 M.C.Maj, B.Singh, and R.S.Gupta (2002).
Pentavalent ions dependency is a conserved property of adenosine kinase from diverse sources: identification of a novel motif implicated in phosphate and magnesium ion binding and substrate inhibition.
  Biochemistry, 41, 4059-4069.  
12235162 M.H.Li, F.Kwok, W.R.Chang, C.K.Lau, J.P.Zhang, S.C.Lo, T.Jiang, and D.C.Liang (2002).
Crystal structure of brain pyridoxal kinase, a novel member of the ribokinase superfamily.
  J Biol Chem, 277, 46385-46390.
PDB codes: 1lhp 1lhr
12457846 R.G.Zhang, J.Grembecka, E.Vinokour, F.Collart, I.Dementieva, W.Minor, and A.Joachimiak (2002).
Structure of Bacillus subtilis YXKO--a member of the UPF0031 family and a putative kinase.
  J Struct Biol, 139, 161-170.
PDB code: 1kyh
11223943 K.Lecoq, I.Belloc, C.Desgranges, and B.Daignan-Fornier (2001).
Role of adenosine kinase in Saccharomyces cerevisiae: identification of the ADO1 gene and study of the mutant phenotypes.
  Yeast, 18, 335-342.  
11173471 Y.X.Gu, Y.D.Liu, Q.Hao, S.E.Ealick, and H.F.Fan (2001).
Direct-method-aided phasing of MAD data.
  Acta Crystallogr D Biol Crystallogr, 57, 250-253.  
11060695 E.A.Kowaluk, and M.F.Jarvis (2000).
Therapeutic potential of adenosine kinase inhibitors.
  Expert Opin Investig Drugs, 9, 551-564.  
10879466 H.Kawasaki, M.Shimaoka, Y.Usuda, and T.Utagawa (2000).
End-product regulation and kinetic mechanism of guanosine-inosine kinase from Escherichia coli.
  Biosci Biotechnol Biochem, 64, 972-979.  
10891066 N.Campobasso, I.I.Mathews, T.P.Begley, and S.E.Ealick (2000).
Crystal structure of 4-methyl-5-beta-hydroxyethylthiazole kinase from Bacillus subtilis at 1.5 A resolution.
  Biochemistry, 39, 7868-7877.
PDB codes: 1c3q 1ekk 1ekq 1esj 1esq
10666633 R.Recacha, A.Talalaev, L.J.DeLucas, and D.Chattopadhyay (2000).
Toxoplasma gondii adenosine kinase: expression, purification, characterization, crystallization and preliminary crystallographic analysis.
  Acta Crystallogr D Biol Crystallogr, 56, 76-78.  
  10794412 W.J.Cook, L.J.DeLucas, and D.Chattopadhyay (2000).
Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.
  Protein Sci, 9, 704-712.
PDB code: 1dgm
10518797 C.Carret, S.Delbecq, G.Labesse, B.Carcy, E.Precigout, K.Moubri, T.P.Schetters, and A.Gorenflot (1999).
Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi.
  Eur J Biochem, 265, 1015-1021.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.