PDBsum entry 1znw

Go to PDB code: 
protein links
Transferase PDB id
Protein chain
182 a.a. *
Waters ×67
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of unliganded form of mycobacterium tuberc guanylate kinase
Structure: Guanylate kinase. Chain: a. Synonym: gmp kinase. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: gmk (rv1389). Expressed in: escherichia coli. Expression_system_taxid: 562.
2.10Å     R-factor:   0.193     R-free:   0.220
Authors: G.Hible,P.Christova,L.Renault,E.Seclaman,A.Thompson,E.Girard H.Munier-Lehmann,J.Cherfils
Key ref:
G.Hible et al. (2006). Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase. Proteins, 62, 489-500. PubMed id: 16288457 DOI: 10.1002/prot.20662
12-May-05     Release date:   29-Nov-05    
Go to PROCHECK summary

Protein chain
P9WKE9  (KGUA_MYCTU) -  Guanylate kinase
208 a.a.
182 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Guanylate kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + GMP = ADP + GDP
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     growth   4 terms 
  Biochemical function     nucleotide binding     9 terms  


DOI no: 10.1002/prot.20662 Proteins 62:489-500 (2006)
PubMed id: 16288457  
Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase.
G.Hible, P.Christova, L.Renault, E.Seclaman, A.Thompson, E.Girard, H.Munier-Lehmann, J.Cherfils.
Bacterial nucleoside monophosphate (NMP) kinases, which convert NMPs to nucleoside diphosphates (NDP), are investigated as potential antibacterial targets against pathogenic bacteria. Herein, we report the biochemical and structural characterization of GMP kinase from Mycobacterium tuberculosis (GMPKMt). GMPKMt is a monomer with an unusual specificity for ATP as a phosphate donor, a lower catalytic efficiency compared with eukaryotic GMPKs, and it carries two redox-sensitive cysteines in the central CORE domain. These properties were analyzed in the light of the high-resolution crystal structures of unbound, GMP-bound, and GDP-bound GMPKMt. The latter structure was obtained in both an oxidized form, in which the cysteines form a disulfide bridge, and a reduced form which is expected to correspond to the physiological enzyme. GMPKMt has a modular domain structure as most NMP kinases. However, it departs from eukaryotic GMPKs by the unusual conformation of its CORE domain, and by its partially open LID and GMP-binding domains which are the same in the apo-, GMP-bound, and GDP-bound forms. GMPKMt also features a unique GMP binding site which is less close-packed than that of mammalian GMPKs, and in which the replacement of a critical tyrosine by a serine removes a catalytic interaction. In contrast, the specificity of GMPKMt for ATP may be a general feature of GMPKs because of an invariant structural motif that recognizes the adenine base. Altogether, differences in domain dynamics and GMP binding between GMPKMt and mammalian GMPKs should reveal clues for the design of GMPKMt-specific inhibitors.
  Selected figure(s)  
Figure 3.
Figure 3. Structure and closure of the GMPK[Mt] domains. a: Superposition of the GMP, CORE, and LID domains of GMPK[Mt]-GMP (in yellow) with the corresponding domains from apo-GMPK[Sc] (PDB entry code 1EX6) or GMPK[Mm]-GMP-ADP (PDB entry code 1LVG). The redox-sensitive cysteines in the CORE domain are shown in orange. Orientations are similar to that in Figure 2a except for the LID domain. b: Comparison of domain closure between the GMPK[Mt] structures and apo- (left) and GMP-bound (right) structures of GMPK[Sc]. GMPK[Mt] is in yellow, GMPK[Sc] in gray (PDB entry codes for apo- and GMP-bound GMPK[Sc] structures are 1EX6 and 1EX7). Note that the GMP domain in GMPK[Mt] is more open than in GMPK[Sc]-GMP and more closed than in apo-GMPK[Sc].
Figure 4.
Figure 4. The GMP and GDP binding site. a: Close-up view of GMP binding site in the GMPK[Mt]-GMP structure. The GMP domain is in blue, the CORE domain in green. Hydrogen bonds are in dotted lines. b: Comparison of GMP/enzyme interactions in mycobacterial GMPK[Mt]-GMP (in yellow) and mammalian GMPK[Mm]-GMP-ADP (in gray). Superpositions are on GMP and the GMP-interacting residues from both structures. c: Comparison of GMP (yellow) and GDP (red) bound to GMPK[Mt].
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2006, 62, 489-500) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21149268 G.Labesse, K.Benkali, I.Salard-Arnaud, A.M.Gilles, and H.Munier-Lehmann (2011).
Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation.
  Nucleic Acids Res, 39, 3458-3472.
PDB code: 3nwy
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.  
19353597 O.Delalande, N.Férey, G.Grasseau, and M.Baaden (2009).
Complex molecular assemblies at hand via interactive simulations.
  J Comput Chem, 30, 2375-2387.  
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
  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
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 code is shown on the right.