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Transferase PDB id
1lvg
Jmol
Contents
Protein chain
190 a.a. *
Ligands
ADP
5GP
Metals
__K
Waters ×197
* Residue conservation analysis
PDB id:
1lvg
Name: Transferase
Title: Crystal structure of mouse guanylate kinase in complex with gmp and adp
Structure: Guanylate kinase. Chain: a. Synonym: gmp kinase. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.10Å     R-factor:   0.188     R-free:   0.231
Authors: N.Sekulic,L.Shuvalova,O.Spangenberg,M.Konrad,A.Lavie
Key ref:
N.Sekulic et al. (2002). Structural characterization of the closed conformation of mouse guanylate kinase. J Biol Chem, 277, 30236-30243. PubMed id: 12036965 DOI: 10.1074/jbc.M204668200
Date:
28-May-02     Release date:   11-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q64520  (KGUA_MOUSE) -  Guanylate kinase
Seq:
Struc: 		198 a.a.
190 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.4.8  - Guanylate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + GMP = ADP + GDP
ATP
 +
GMP
Bound ligand (Het Group name = 5GP)
corresponds exactly 		=
ADP
Bound ligand (Het Group name = ADP)
corresponds exactly 		+ GDP
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     purine nucleotide metabolic process   1 term 
  Biochemical function     nucleotide binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M204668200 J Biol Chem 277:30236-30243 (2002)
PubMed id: 12036965  
 
 
Structural characterization of the closed conformation of mouse guanylate kinase.
N.Sekulic, L.Shuvalova, O.Spangenberg, M.Konrad, A.Lavie.
 
  ABSTRACT  
 
Guanylate kinase (GMPK) is a nucleoside monophosphate kinase that catalyzes the reversible phosphoryl transfer from ATP to GMP to yield ADP and GDP. In addition to phosphorylating GMP, antiviral prodrugs such as acyclovir, ganciclovir, and carbovir and anticancer prodrugs such as the thiopurines are dependent on GMPK for their activation. Hence, structural information on mammalian GMPK could play a role in the design of improved antiviral and antineoplastic agents. Here we present the structure of the mouse enzyme in an abortive complex with the nucleotides ADP and GMP, refined at 2.1 A resolution with a final crystallographic R factor of 0.19 (R(free) = 0.23). Guanylate kinase is a member of the nucleoside monophosphate (NMP) kinase family, a family of enzymes that despite having a low primary structure identity share a similar fold, which consists of three structurally distinct regions termed the CORE, LID, and NMP-binding regions. Previous studies on the yeast enzyme have shown that these parts move as rigid bodies upon substrate binding. It has been proposed that consecutive binding of substrates leads to "closing" of the active site bringing the NMP-binding and LID regions closer to each other and to the CORE region. Our structure, which is the first of any guanylate kinase with both substrates bound, supports this hypothesis. It also reveals the binding site of ATP and implicates arginines 44, 137, and 148 (in addition to the invariant P-loop lysine) as candidates for catalyzing the chemical step of the phosphoryl transfer.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Overlay of each individual region from the three GMPK structures. Calculations of superposition matrices were done according to the residues specified in text, with the largest RMSD for all three regions being between mGMPK[GMP-ADP] and yGMPK[apo]. a, overlay of LID region. b, overlay of NMP-binding region. c, overlay of CORE region. Highest RMSD values were: for the CORE region, 1.62 Å; for the NMP-binding region, 0.76 Å; and for the LID region, 0.86 Å. The regions from yGMPK[apo] are displayed in green, those from yGMPK[GMP] are in blue, and those from mGMPK[GMP-ADP] are in magenta. 		Figure 3.
Fig. 3. Three conformational states of GMPK. Overlays of yGMPK [apo] (green), yGMPK[GMP] (blue), and mGMPK[GMP-ADP] (magenta) are shown. The nucleotide-dependent conformational states are open in the apo-structure, partially closed in the presence of GMP, and fully closed in the presence of GMP and ADP.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 30236-30243) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360614 M.Kandeel, and Y.Kitade (2011).
Binding dynamics and energetic insight into the molecular forces driving nucleotide binding by guanylate kinase.
  J Mol Recognit, 24, 322-332.  
21081090 S.Sacquin-Mora, O.Delalande, and M.Baaden (2010).
Functional modes and residue flexibility control the anisotropic response of guanylate kinase to mechanical stress.
  Biophys J, 99, 3412-3419.  
19136674 A.Ardiani, A.Goyke, and M.E.Black (2009).
Mutations at serine 37 in mouse guanylate kinase confer resistance to 6-thioguanine.
  Protein Eng Des Sel, 22, 225-232.  
18178651 C.Stanley, S.Krueger, V.A.Parsegian, and D.C.Rau (2008).
Protein structure and hydration probed by SANS and osmotic stress.
  Biophys J, 94, 2777-2789.  
17542990 A.Ofiteru, N.Bucurenci, E.Alexov, T.Bertrand, P.Briozzo, H.Munier-Lehmann, and A.M.Gilles (2007).
Structural and functional consequences of single amino acid substitutions in the pyrimidine base binding pocket of Escherichia coli CMP kinase.
  FEBS J, 274, 3363-3373.
PDB codes: 2fem 2feo
17142284 B.Choi, and G.Zocchi (2007).
Guanylate kinase, induced fit, and the allosteric spring probe.
  Biophys J, 92, 1651-1658.  
17672887 G.Mayr, F.S.Domingues, and P.Lackner (2007).
Comparative analysis of protein structure alignments.
  BMC Struct Biol, 7, 50.  
17220895 M.L.Reese, S.Dakoji, D.S.Bredt, and V.Dötsch (2007).
The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a.
  Nat Struct Mol Biol, 14, 155-163.  
17276460 N.Sekulic, K.Dietrich, I.Paarmann, S.Ort, M.Konrad, and A.Lavie (2007).
Elucidation of the active conformation of the APS-kinase domain of human PAPS synthetase 1.
  J Mol Biol, 367, 488-500.
PDB codes: 2ofw 2ofx
17096593 D.Korkin, F.P.Davis, F.Alber, T.Luong, M.Y.Shen, V.Lucic, M.B.Kennedy, and A.Sali (2006).
Structural modeling of protein interactions by analogy: application to PSD-95.
  PLoS Comput Biol, 2, e153.  
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
  17012781 K.El Omari, B.Dhaliwal, M.Lockyer, I.Charles, A.R.Hawkins, and D.K.Stammers (2006).
Structure of Staphylococcus aureus guanylate monophosphate kinase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 949-953.
PDB code: 2j41
16522804 M.Kotaka, B.Dhaliwal, J.Ren, C.E.Nichols, R.Angell, M.Lockyer, A.R.Hawkins, and D.K.Stammers (2006).
Structures of S. aureus thymidylate kinase reveal an atypical active site configuration and an intermediate conformational state upon substrate binding.
  Protein Sci, 15, 774-784.
PDB codes: 2ccg 2ccj 2cck
14997573 I.L.de La Sierra-Gallay, B.Collinet, M.Graille, S.Quevillon-Cheruel, D.Liger, P.Minard, K.Blondeau, G.Henckes, R.Aufrère, N.Leulliot, C.Z.Zhou, I.Sorel, J.L.Ferrer, A.Poupon, J.Janin, and H.van Tilbeurgh (2004).
Crystal structure of the YGR205w protein from Saccharomyces cerevisiae: close structural resemblance to E. coli pantothenate kinase.
  Proteins, 54, 776-783.
PDB code: 1odf
15130468 N.N.Suzuki, K.Koizumi, M.Fukushima, A.Matsuda, and F.Inagaki (2004).
Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
  Structure, 12, 751-764.
PDB codes: 1udw 1uei 1uej 1ufq 1uj2
15134636 Y.Opatowsky, C.C.Chen, K.P.Campbell, and J.A.Hirsch (2004).
Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain.
  Neuron, 42, 387-399.
PDB code: 1t3l
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.