PDBsum entry 4ake

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Phosphotransferase PDB id
Protein chains
214 a.a. *
Waters ×147
* Residue conservation analysis
PDB id:
Name: Phosphotransferase
Title: Adenylate kinase
Structure: Adenylate kinase. Chain: a, b. Synonym: atp\:amp phosphotransferase, myokinase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Cellular_location: cytosol. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.20Å     R-factor:   0.183    
Authors: G.J.Schlauderer,G.E.Schulz
Key ref:
C.W.Müller et al. (1996). Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding. Structure, 4, 147-156. PubMed id: 8805521 DOI: 10.1016/S0969-2126(96)00018-4
29-Dec-95     Release date:   10-Jun-96    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P69441  (KAD_ECOLI) -  Adenylate kinase
214 a.a.
214 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Adenylate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + AMP = 2 ADP
= 2 × ADP
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     AMP salvage   10 terms 
  Biochemical function     nucleotide binding     10 terms  


DOI no: 10.1016/S0969-2126(96)00018-4 Structure 4:147-156 (1996)
PubMed id: 8805521  
Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
C.W.Müller, G.J.Schlauderer, J.Reinstein, G.E.Schulz.
BACKGROUND: Adenylate kinases undergo large conformational changes during their catalytic cycle. Because these changes have been studied by comparison of structures from different species, which share approximately one-third of their residues, only rough descriptions have been possible to date. RESULTS: We have solved the structure of unligated adenylate kinase from Escherichia coli at 2.2 degree resolution and compared it with the high-resolution structure of the same enzyme ligated with an inhibitor mimicking both substrates, ATP and AMP. This comparison shows that, upon substrate binding, the enzyme increases its chain mobility in a region remote from the active center. As this region 'solidifies' again on substrate release, we propose that it serves as a 'counterweight' balancing the substrate binding energy. CONCLUSION: The comparison of two very different conformations of the same polypeptide chain revealed kinematic details of the catalytic cycle. Moreover, it indicated that there exists an energetic counterweight compensating the substrate binding energy required for specificity. This counterweight prevents the enzyme from dropping into a rate-reducing energy well along the reaction coordinate.
  Selected figure(s)  
Figure 3.
Figure 3. Stereo diagram illustrating the molecular packing in the a–c plane of the P1 crystals (c horizontal). The slightly asymmetric contacts between the LID domains of molecule I (left) and molecule II (right) are visible. Figure 3. Stereo diagram illustrating the molecular packing in the a–c plane of the P1 crystals (c horizontal). The slightly asymmetric contacts between the LID domains of molecule I (left) and molecule II (right) are visible.
Figure 8.
Figure 8. Kinematics at hinge H6 in the movement of domain LID from an ‘open’ to the ‘closed’ state as derived from a molecular dynamics simulation using X-PLOR [19]. The average (φ, ψ) pathways of the ‘trigger’ residues are plotted with dots at 0.5 ps intervals: S, start in the apo-AK[eco] structure; E, end of simulated pathway; T, target value in the AK[eco]:Ap[5]A structure. The averages are from 10 simulations all of which run along similar pathways. The allowed regions [18] of the (φ, ψ) plot are indicated by dotted lines. Figure 8. Kinematics at hinge H6 in the movement of domain LID from an ‘open’ to the ‘closed’ state as derived from a molecular dynamics simulation using X-PLOR [[3]19]. The average (φ, ψ) pathways of the ‘trigger’ residues are plotted with dots at 0.5 ps intervals: S, start in the apo-AK[eco] structure; E, end of simulated pathway; T, target value in the AK[eco]:Ap[5]A structure. The averages are from 10 simulations all of which run along similar pathways. The allowed regions [[4]18] of the (φ, ψ) plot are indicated by dotted lines.
  The above figures are reprinted by permission from Cell Press: Structure (1996, 4, 147-156) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20821240 A.Mukhopadhyay, A.V.Kladova, S.A.Bursakov, O.Y.Gavel, J.J.Calvete, V.L.Shnyrov, I.Moura, J.J.Moura, M.J.Romão, and J.Trincão (2011).
Crystal structure of the zinc-, cobalt-, and iron-containing adenylate kinase from Desulfovibrio gigas: a novel metal-containing adenylate kinase from Gram-negative bacteria.
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PDB codes: 2xb4 3l0p 3l0s
21261390 B.Jana, B.V.Adkar, R.Biswas, and B.Bagchi (2011).
Dynamic coupling between the LID and NMP domain motions in the catalytic conversion of ATP and AMP to ADP by adenylate kinase.
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Identification of functional motions in the adenylate kinase (ADK) protein family by computational hybrid approaches.
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21183988 Y.W.Tan, and H.Yang (2011).
Seeing the forest for the trees: fluorescence studies of single enzymes in the context of ensemble experiments.
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Large-scale comparison of protein essential dynamics from molecular dynamics simulations and coarse-grained normal mode analyses.
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Structural dynamics of bio-macromolecules by NMR: the slowly relaxing local structure approach.
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20331978 G.W.Buchko, H.Robinson, J.Abendroth, B.L.Staker, and P.J.Myler (2010).
Structural characterization of Burkholderia pseudomallei adenylate kinase (Adk): profound asymmetry in the crystal structure of the 'open' state.
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PDB code: 3gmt
20954241 G.Williams, and A.J.Toon (2010).
Protein folding pathways and state transitions described by classical equations of motion of an elastic network model.
  Protein Sci, 19, 2451-2461.  
20617196 H.Dong, S.Qin, and H.X.Zhou (2010).
Effects of macromolecular crowding on protein conformational changes.
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21081091 J.B.Brokaw, and J.W.Chu (2010).
On the roles of substrate binding and hinge unfolding in conformational changes of adenylate kinase.
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20890288 L.R.Masterson, C.Cheng, T.Yu, M.Tonelli, A.Kornev, S.S.Taylor, and G.Veglia (2010).
Dynamics connect substrate recognition to catalysis in protein kinase A.
  Nat Chem Biol, 6, 821-828.
PDB code: 3o7l
20594332 M.Mechelke, and M.Habeck (2010).
Robust probabilistic superposition and comparison of protein structures.
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20205445 R.G.Coleman, and K.A.Sharp (2010).
Protein pockets: inventory, shape, and comparison.
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20590215 R.I.Cukier (2010).
How many atoms are required to characterize accurately trajectory fluctuations of a protein?
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19408277 R.S.Sedeh, M.Bathe, and K.J.Bathe (2010).
The subspace iteration method in protein normal mode analysis.
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20232415 S.Khan, and M.Vihinen (2010).
Performance of protein stability predictors.
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20163968 S.Yin, and J.A.Loo (2010).
Elucidating the site of protein-ATP binding by top-down mass spectrometry.
  J Am Soc Mass Spectrom, 21, 899-907.  
21081909 U.Olsson, and M.Wolf-Watz (2010).
Overlap between folding and functional energy landscapes for adenylate kinase conformational change.
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18712827 A.D.Schuyler, R.L.Jernigan, P.K.Qasba, B.Ramakrishnan, and G.S.Chirikjian (2009).
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Computation of conformational transitions in proteins by virtual atom molecular mechanics as validated in application to adenylate kinase.
  Proc Natl Acad Sci U S A, 106, 15673-15678.  
18798562 A.L.Olson, H.Yao, T.J.Herdendorf, H.M.Miziorko, S.Hannongbua, P.Saparpakorn, S.Cai, and D.S.Sem (2009).
Substrate induced structural and dynamics changes in human phosphomevalonate kinase and implications for mechanism.
  Proteins, 75, 127-138.  
19708737 J.N.Stember, and W.Wriggers (2009).
Bend-twist-stretch model for coarse elastic network simulation of biomolecular motion.
  J Chem Phys, 131, 074112.  
19131951 L.Bordoli, F.Kiefer, K.Arnold, P.Benkert, J.Battey, and T.Schwede (2009).
Protein structure homology modeling using SWISS-MODEL workspace.
  Nat Protoc, 4, 1.  
19751742 O.Beckstein, E.J.Denning, J.R.Perilla, and T.B.Woolf (2009).
Zipping and unzipping of adenylate kinase: atomistic insights into the ensemble of open<-->closed transitions.
  J Mol Biol, 394, 160-176.  
19805185 T.P.Schrank, D.W.Bolen, and V.J.Hilser (2009).
Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins.
  Proc Natl Acad Sci U S A, 106, 16984-16989.
PDB codes: 3hpq 3hpr
17933762 B.H.Dessailly, M.F.Lensink, C.A.Orengo, and S.J.Wodak (2008).
LigASite--a database of biologically relevant binding sites in proteins with known apo-structures.
  Nucleic Acids Res, 36, D667-D673.  
18931260 F.Pontiggia, A.Zen, and C.Micheletti (2008).
Small- and large-scale conformational changes of adenylate kinase: a molecular dynamics study of the subdomain motion and mechanics.
  Biophys J, 95, 5901-5912.  
18004789 M.Kosloff, and R.Kolodny (2008).
Sequence-similar, structure-dissimilar protein pairs in the PDB.
  Proteins, 71, 891-902.  
18676657 N.Kantarci-Carsibasi, T.Haliloglu, and P.Doruker (2008).
Conformational transition pathways explored by Monte Carlo simulation integrated with collective modes.
  Biophys J, 95, 5862-5873.  
17998210 P.C.Whitford, S.Gosavi, and J.N.Onuchic (2008).
Conformational Transitions in Adenylate Kinase: ALLOSTERIC COMMUNICATION REDUCES MISLIGATION.
  J Biol Chem, 283, 2042-2048.  
18572416 R.K.Tan, B.Devkota, and S.C.Harvey (2008).
YUP.SCX: coaxing atomic models into medium resolution electron density maps.
  J Struct Biol, 163, 163-174.  
17640073 S.Kirillova, J.Cortés, A.Stefaniu, and T.Siméon (2008).
An NMA-guided path planning approach for computing large-amplitude conformational changes in proteins.
  Proteins, 70, 131-143.  
17299745 C.Snow, G.Qi, and S.Hayward (2007).
Essential dynamics sampling study of adenylate kinase: comparison to citrate synthase and implication for the hinge and shear mechanisms of domain motions.
  Proteins, 67, 325-337.  
17286863 J.Gu, and P.E.Bourne (2007).
Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2.
  BMC Bioinformatics, 8, 45.  
17704151 J.W.Chu, and G.A.Voth (2007).
Coarse-grained free energy functions for studying protein conformational changes: a double-well network model.
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18026086 K.A.Henzler-Wildman, V.Thai, M.Lei, M.Ott, M.Wolf-Watz, T.Fenn, E.Pozharski, M.A.Wilson, G.A.Petsko, M.Karplus, C.G.Hübner, and D.Kern (2007).
Intrinsic motions along an enzymatic reaction trajectory.
  Nature, 450, 838-844.
PDB codes: 2rgx 2rh5
17217965 P.C.Whitford, O.Miyashita, Y.Levy, and J.N.Onuchic (2007).
Conformational transitions of adenylate kinase: switching by cracking.
  J Mol Biol, 366, 1661-1671.  
16839194 J.Gu, M.Gribskov, and P.E.Bourne (2006).
Wiggle-predicting functionally flexible regions from primary sequence.
  PLoS Comput Biol, 2, e90.  
15747033 G.Yang, X.Yu, Z.Wu, J.Xu, L.Song, H.Zhang, X.Hu, N.Zheng, L.Guo, J.Xu, J.Dai, C.Ji, S.Gu, and K.Ying (2005).
Molecular cloning and characterization of a novel adenylate kinase 3 gene from Clonorchis sinensis.
  Parasitol Res, 95, 406-412.  
15521058 H.Krishnamurthy, H.Lou, A.Kimple, C.Vieille, and R.I.Cukier (2005).
Associative mechanism for phosphoryl transfer: a molecular dynamics simulation of Escherichia coli adenylate kinase complexed with its substrates.
  Proteins, 58, 88.  
15281134 D.B.Sherman, S.Zhang, J.B.Pitner, and A.Tropsha (2004).
Evaluation of the relative stability of liganded versus ligand-free protein conformations using Simplicial Neighborhood Analysis of Protein Packing (SNAPP) method.
  Proteins, 56, 828-838.  
15100224 E.Bae, and G.N.Phillips (2004).
Structures and analysis of highly homologous psychrophilic, mesophilic, and thermophilic adenylate kinases.
  J Biol Chem, 279, 28202-28208.
PDB codes: 1p3j 1s3g
15116357 M.Lei, M.I.Zavodszky, L.A.Kuhn, and M.F.Thorpe (2004).
Sampling protein conformations and pathways.
  J Comput Chem, 25, 1133-1148.  
15334070 M.Wolf-Watz, V.Thai, K.Henzler-Wildman, G.Hadjipavlou, E.Z.Eisenmesser, and D.Kern (2004).
Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair.
  Nat Struct Mol Biol, 11, 945-949.  
15382240 N.A.Temiz, E.Meirovitch, and I.Bahar (2004).
Escherichia coli adenylate kinase dynamics: comparison of elastic network model modes with mode-coupling (15)N-NMR relaxation data.
  Proteins, 57, 468-480.  
12454011 A.Haouz, V.Vanheusden, H.Munier-Lehmann, M.Froeyen, P.Herdewijn, S.Van Calenbergh, and M.Delarue (2003).
Enzymatic and structural analysis of inhibitors designed against Mycobacterium tuberculosis thymidylate kinase. New insights into the phosphoryl transfer mechanism.
  J Biol Chem, 278, 4963-4971.
PDB codes: 1mrn 1mrs
12573349 C.B.Gambacorti-Passerini, R.H.Gunby, R.Piazza, A.Galietta, R.Rostagno, and L.Scapozza (2003).
Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias.
  Lancet Oncol, 4, 75-85.  
12036965 N.Sekulic, L.Shuvalova, O.Spangenberg, M.Konrad, and A.Lavie (2002).
Structural characterization of the closed conformation of mouse guanylate kinase.
  J Biol Chem, 277, 30236-30243.
PDB code: 1lvg
12068016 S.K.Singh, O.V.Kurnasov, B.Chen, H.Robinson, N.V.Grishin, A.L.Osterman, and H.Zhang (2002).
Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
  J Biol Chem, 277, 33291-33299.
PDB code: 1lw7
12009888 Y.E.Shapiro, E.Kahana, V.Tugarinov, Z.Liang, J.H.Freed, and E.Meirovitch (2002).
Domain flexibility in ligand-free and inhibitor-bound Escherichia coli adenylate kinase based on a mode-coupling analysis of 15N spin relaxation.
  Biochemistry, 41, 6271-6281.  
11159387 B.Speelman, B.R.Brooks, and C.B.Post (2001).
Molecular dynamics simulations of human rhinovirus and an antiviral compound.
  Biophys J, 80, 121-129.  
11325743 S.Kumar, Y.Y.Sham, C.J.Tsai, and R.Nussinov (2001).
Protein folding and function: the N-terminal fragment in adenylate kinase.
  Biophys J, 80, 2439-2454.  
10835366 T.Izard, and J.Ellis (2000).
The crystal structures of chloramphenicol phosphotransferase reveal a novel inactivation mechanism.
  EMBO J, 19, 2690-2700.
PDB codes: 1qhn 1qhs 1qhx 1qhy
10542226 B.D.Pilger, R.Perozzo, F.Alber, C.Wurth, G.Folkers, and L.Scapozza (1999).
Substrate diversity of herpes simplex virus thymidine kinase. Impact Of the kinematics of the enzyme.
  J Biol Chem, 274, 31967-31973.  
10387103 B.Turk, R.Awad, E.V.Usova, I.Björk, and S.Eriksson (1999).
A pre-steady-state kinetic analysis of substrate binding to human recombinant deoxycytidine kinase: a model for nucleoside kinase action.
  Biochemistry, 38, 8555-8561.  
10450084 S.Hayward (1999).
Structural principles governing domain motions in proteins.
  Proteins, 36, 425-435.  
  10593256 S.Kumar, B.Ma, C.J.Tsai, H.Wolfson, and R.Nussinov (1999).
Folding funnels and conformational transitions via hinge-bending motions.
  Cell Biochem Biophys, 31, 141-164.  
9548738 D.H.Harrison, J.A.Runquist, A.Holub, and H.M.Miziorko (1998).
The crystal structure of phosphoribulokinase from Rhodobacter sphaeroides reveals a fold similar to that of adenylate kinase.
  Biochemistry, 37, 5074-5085.
PDB code: 1a7j
9715904 M.B.Berry, and G.N.Phillips (1998).
Crystal structures of Bacillus stearothermophilus adenylate kinase with bound Ap5A, Mg2+ Ap5A, and Mn2+ Ap5A reveal an intermediate lid position and six coordinate octahedral geometry for bound Mg2+ and Mn2+.
  Proteins, 32, 276-288.
PDB codes: 1zin 1zio 1zip
9668095 S.Burlacu-Miron, V.Perrier, A.M.Gilles, E.Pistotnik, and C.T.Craescu (1998).
Structural and energetic factors of the increased thermal stability in a genetically engineered Escherichia coli adenylate kinase.
  J Biol Chem, 273, 19102-19107.  
9668094 V.Perrier, S.Burlacu-Miron, S.Bourgeois, W.K.Surewicz, and A.M.Gilles (1998).
Genetically engineered zinc-chelating adenylate kinase from Escherichia coli with enhanced thermal stability.
  J Biol Chem, 273, 19097-19101.  
9004553 H.W.Behrends, G.Folkers, and A.G.Beck-Sickinger (1997).
A new approach to secondary structure evaluation: secondary structure prediction of porcine adenylate kinase and yeast guanylate kinase by CD spectroscopy of overlapping synthetic peptide segments.
  Biopolymers, 41, 213-231.  
  8976551 G.S.Prasad, E.A.Stura, D.E.McRee, G.S.Laco, C.Hasselkus-Light, J.H.Elder, and C.D.Stout (1996).
Crystal structure of dUTP pyrophosphatase from feline immunodeficiency virus.
  Protein Sci, 5, 2429-2437.
PDB code: 1dut
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