PDBsum entry 2aky

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Adenylate kinase PDB id
Protein chain
218 a.a. *
Waters ×459
* Residue conservation analysis
PDB id:
Name: Adenylate kinase
Title: High-resolution structures of adenylate kinase from yeast ligated with inhibitor ap5a, showing the pathway of phosphoryl transfer
Structure: Adenylate kinase. Chain: a. Synonym: atp\:amp phosphotransferase, myokinase. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Strain: red star, milwaukee. Cellular_location: cytosol. Expressed in: escherichia coli. Expression_system_taxid: 562
1.96Å     R-factor:   0.176    
Authors: U.Abele,G.E.Schulz
Key ref:
U.Abele and G.E.Schulz (1995). High-resolution structures of adenylate kinase from yeast ligated with inhibitor Ap5A, showing the pathway of phosphoryl transfer. Protein Sci, 4, 1262-1271. PubMed id: 7670369 DOI: 10.1002/pro.5560040702
28-Jul-95     Release date:   14-Nov-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P07170  (KAD1_YEAST) -  Adenylate kinase
222 a.a.
218 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Adenylate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + AMP = 2 ADP
Bound ligand (Het Group name = AP5)
matches with 54.00% similarity
= 2 × ADP
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   5 terms 
  Biological process     nucleobase-containing compound metabolic process   8 terms 
  Biochemical function     nucleotide binding     7 terms  


DOI no: 10.1002/pro.5560040702 Protein Sci 4:1262-1271 (1995)
PubMed id: 7670369  
High-resolution structures of adenylate kinase from yeast ligated with inhibitor Ap5A, showing the pathway of phosphoryl transfer.
U.Abele, G.E.Schulz.
The structure of adenylate kinase from yeast ligated with the two-substrate-mimicking inhibitor Ap5A and Mg2+ has been refined to 1.96 A resolution. In addition, the refined structure of the same complex with a bound imidazole molecule replacing Mg2+ has been determined at 1.63 A. These structures indicate that replacing Mg2+ by imidazole disturbs the water structure and thus the complex. A comparison with the G-proteins shows that Mg2+ is exactly at the same position with respect to the phosphates. However, although the Mg2+ ligand sphere of the G-proteins is a regular octahedron containing peptide ligands, the reported adenylate kinase has no such ligands and an open octahedron leaving space for the Mg2+ to accompany the transferred phosphoryl group. A superposition of the known crystalline and therefore perturbed phosphoryl transfer geometries in the adenylate kinases demonstrates that all of them are close to the start of the forward reaction with bound ATP and AMP. Averaging all observed perturbed structures gives rise to a close approximation of the transition state, indicating in general how to establish an elusive transition state geometry. The average shows that the in-line phosphoryl transfer is associative, because there is no space for a dissociative metaphosphate intermediate. As a side result, the secondary dipole interaction in the alpha-helices of both protein structures has been quantified.
  Selected figure(s)  
Figure 4.
Fig. 4. Relationbetweenthelengthsofprimaryandsecondaryhydro- genbonds in a-helicesasreferredtothedonoramdeatposition . The plotcontainsalla-helicalH-bonds(Fig. 3) frombothreportedstruc- tures.Averageangles N,-H,. . .0,-4 and N,-H,. . .0,-3 are 161" and I1 I, respectively.
Figure 6.
Fig. 6. BindingofImandMg2+in AK,,, ligated with Ap,A.Mostresidues andtwowatermoleulesarelabeled. Chaincutsaremarked by dots. A: Posi- tion f Mg2+(dot) in an extendedwater cluster.Detailedenvronment of Mg2+ is showninFigures8Band9. : Bind- ing of s suspended between hetird phosphteandAsp89.Imidazoledis- turbsappreciablythewateretworkat theactivecenter.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1995, 4, 1262-1271) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21081909 U.Olsson, and M.Wolf-Watz (2010).
Overlap between folding and functional energy landscapes for adenylate kinase conformational change.
  Nat Commun, 1, 111.  
19398430 M.Hernandez, D.Ghersi, and R.Sanchez (2009).
SITEHOUND-web: a server for ligand binding site identification in protein structures.
  Nucleic Acids Res, 37, W413-W416.  
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.  
19130895 R.Liu, A.L.Ström, J.Zhai, J.Gal, S.Bao, W.Gong, and H.Zhu (2009).
Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase.
  Int J Biochem Cell Biol, 41, 1371-1380.  
18805924 Q.Dong, C.O.Randak, and M.J.Welsh (2008).
A mutation in CFTR modifies the effects of the adenylate kinase inhibitor Ap5A on channel gating.
  Biophys J, 95, 5178-5185.  
18433446 S.Gauthier, F.Coulpier, L.Jourdren, M.Merle, S.Beck, M.Konrad, B.Daignan-Fornier, and B.Pinson (2008).
Co-regulation of yeast purine and phosphate pathways in response to adenylic nucleotide variations.
  Mol Microbiol, 68, 1583-1594.  
17154432 A.K.Hirsch, F.R.Fischer, and F.Diederich (2007).
Phosphate recognition in structural biology.
  Angew Chem Int Ed Engl, 46, 338-352.  
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.  
17698003 J.A.Khan, S.Xiang, and L.Tong (2007).
Crystal structure of human nicotinamide riboside kinase.
  Structure, 15, 1005-1013.
PDB codes: 2qg6 2ql6
16510969 F.Fabiola, A.Korostelev, and M.S.Chapman (2006).
Bias in cross-validated free R factors: mitigation of the effects of non-crystallographic symmetry.
  Acta Crystallogr D Biol Crystallogr, 62, 227-238.  
16288457 G.Hible, P.Christova, L.Renault, E.Seclaman, A.Thompson, E.Girard, H.Munier-Lehmann, and J.Cherfils (2006).
Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase.
  Proteins, 62, 489-500.
PDB codes: 1znw 1znx 1zny 1znz
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.  
15695358 S.Huang, and E.K.O'Shea (2005).
A systematic high-throughput screen of a yeast deletion collection for mutants defective in PHO5 regulation.
  Genetics, 169, 1859-1871.  
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.  
15377393 W.Cai, J.Pei, and N.V.Grishin (2004).
Reconstruction of ancestral protein sequences and its applications.
  BMC Evol Biol, 4, 33.  
14573872 L.Yu, J.Mack, P.J.Hajduk, S.J.Kakavas, A.Y.Saiki, C.G.Lerner, and E.T.Olejniczak (2003).
Solution structure and function of an essential CMP kinase of Streptococcus pneumoniae.
  Protein Sci, 12, 2613-2621.
PDB code: 1q3t
12110598 L.K.Wang, C.D.Lima, and S.Shuman (2002).
Structure and mechanism of T4 polynucleotide kinase: an RNA repair enzyme.
  EMBO J, 21, 3873-3880.
PDB code: 1ly1
11842120 L.K.Wang, and S.Shuman (2002).
Mutational analysis defines the 5'-kinase and 3'-phosphatase active sites of T4 polynucleotide kinase.
  Nucleic Acids Res, 30, 1073-1080.  
11371198 R.A.Farley, E.Elquza, J.Müller-Ehmsen, D.J.Kane, A.K.Nagy, V.N.Kasho, and L.D.Faller (2001).
18O-exchange evidence that mutations of arginine in a signature sequence for P-type pumps affect inorganic phosphate binding.
  Biochemistry, 40, 6361-6370.  
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.  
11369852 T.Krell, J.Maclean, D.J.Boam, A.Cooper, M.Resmini, K.Brocklehurst, S.M.Kelly, N.C.Price, A.J.Lapthorn, and J.R.Coggins (2001).
Biochemical and X-ray crystallographic studies on shikimate kinase: the important structural role of the P-loop lysine.
  Protein Sci, 10, 1137-1149.
PDB code: 1e6c
10677210 I.J.MacRae, I.H.Segel, and A.J.Fisher (2000).
Crystal structure of adenosine 5'-phosphosulfate kinase from Penicillium chrysogenum.
  Biochemistry, 39, 1613-1621.
PDB code: 1d6j
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
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
10873853 N.Ostermann, I.Schlichting, R.Brundiers, M.Konrad, J.Reinstein, T.Veit, R.S.Goody, and A.Lavie (2000).
Insights into the phosphoryltransfer mechanism of human thymidylate kinase gained from crystal structures of enzyme complexes along the reaction coordinate.
  Structure, 8, 629-642.
PDB codes: 1e2d 1e2e 1e2f 1e2g 1e2q
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
10928966 W.M.Chan, W.Welch, and R.Sitsapesan (2000).
Structural factors that determine the ability of adenosine and related compounds to activate the cardiac ryanodine receptor.
  Br J Pharmacol, 130, 1618-1626.  
10736162 Y.Lin, and B.D.Nageswara Rao (2000).
Structural characterization of adenine nucleotides bound to Escherichia coli adenylate kinase. 1. Adenosine conformations by proton two-dimensional transferred nuclear Overhauser effect spectroscopy.
  Biochemistry, 39, 3636-3646.  
10736163 Y.Lin, and B.D.Nageswara Rao (2000).
Structural characterization of adenine nucleotides bound to Escherichia coli adenylate kinase. 2. 31P and 13C relaxation measurements in the presence of cobalt(II) and manganese(II).
  Biochemistry, 39, 3647-3655.  
10508782 C.H.Weber, Y.S.Park, S.Sanker, C.Kent, and M.L.Ludwig (1999).
A prototypical cytidylyltransferase: CTP:glycerol-3-phosphate cytidylyltransferase from bacillus subtilis.
  Structure, 7, 1113-1124.
PDB code: 1coz
10194320 F.Marsolais, M.Laviolette, Y.Kakuta, M.Negishi, L.C.Pedersen, M.Auger, and L.Varin (1999).
3'-Phosphoadenosine 5'-phosphosulfate binding site of flavonol 3-sulfotransferase studied by affinity chromatography and 31P NMR.
  Biochemistry, 38, 4066-4071.  
10394366 R.C.Hillig, L.Renault, I.R.Vetter, T.Drell, A.Wittinghofer, and J.Becker (1999).
The crystal structure of rna1p: a new fold for a GTPase-activating protein.
  Mol Cell, 3, 781-791.
PDB code: 1yrg
  9922246 S.Landais, P.Gounon, C.Laurent-Winter, J.C.Mazié, A.Danchin, O.Bârzu, and H.Sakamoto (1999).
Immunochemical analysis of UMP kinase from Escherichia coli.
  J Bacteriol, 181, 833-840.  
9521686 A.Lavie, M.Konrad, R.Brundiers, R.S.Goody, I.Schlichting, and J.Reinstein (1998).
Crystal structure of yeast thymidylate kinase complexed with the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) at 2.0 A resolution: implications for catalysis and AZT activation.
  Biochemistry, 37, 3677-3686.
PDB code: 3tmk
9562560 A.Matte, L.W.Tari, and L.T.Delbaere (1998).
How do kinases transfer phosphoryl groups?
  Structure, 6, 413-419.  
9843365 I.I.Mathews, M.D.Erion, and S.E.Ealick (1998).
Structure of human adenosine kinase at 1.5 A resolution.
  Biochemistry, 37, 15607-15620.
PDB code: 1bx4
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
  9336829 A.Beyer (1997).
Sequence analysis of the AAA protein family.
  Protein Sci, 6, 2043-2058.  
9428681 K.Wild, R.Grafmüller, E.Wagner, and G.E.Schulz (1997).
Structure, catalysis and supramolecular assembly of adenylate kinase from maize.
  Eur J Biochem, 250, 326-331.
PDB code: 1zak
  9336833 K.Wild, T.Bohner, G.Folkers, and G.E.Schulz (1997).
The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.
  Protein Sci, 6, 2097-2106.
PDB codes: 1vtk 2vtk 3vtk
9129831 N.Murali, Y.Lin, Y.Mechulam, P.Plateau, and B.D.Rao (1997).
Adenosine conformations of nucleotides bound to methionyl tRNA synthetase by transferred nuclear Overhauser effect spectroscopy.
  Biophys J, 72, 2275-2284.  
9201952 V.N.Kasho, M.Stengelin, I.N.Smirnova, and L.D.Faller (1997).
A proposal for the Mg2+ binding site of P-type ion motive ATPases and the mechanism of phosphoryl group transfer.
  Biochemistry, 36, 8045-8052.  
  8670851 A.Teplyakov, P.Sebastiao, G.Obmolova, A.Perrakis, G.S.Brush, M.J.Bessman, and K.S.Wilson (1996).
Crystal structure of bacteriophage T4 deoxynucleotide kinase with its substrates dGMP and ATP.
  EMBO J, 15, 3487-3497.
PDB codes: 1dek 1del
8805521 C.W.Müller, G.J.Schlauderer, J.Reinstein, and G.E.Schulz (1996).
Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
  Structure, 4, 147-156.
PDB code: 4ake
  8868479 G.J.Schlauderer, and G.E.Schulz (1996).
The structure of bovine mitochondrial adenylate kinase: comparison with isoenzymes in other compartments.
  Protein Sci, 5, 434-441.
PDB codes: 1ak2 2ak2
8703943 K.Scheffzek, W.Kliche, L.Wiesmüller, and J.Reinstein (1996).
Crystal structure of the complex of UMP/CMP kinase from Dictyostelium discoideum and the bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-uridyl) pentaphosphate (UP5A) and Mg2+ at 2.2 A: implications for water-mediated specificity.
  Biochemistry, 35, 9716-9727.
PDB codes: 1ukd 1uke
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.