PDBsum entry: 1znx

Transferase

PDB id: 1znx

Contents

Protein chain

182 a.a. *

Ligands

5GP

Waters ×68

* Residue conservation analysis

PDB id:

1znx

Name:

Transferase

Title:

Crystal structure of mycobacterium tuberculosis guanylate ki complex with gmp

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.

Resolution:

2.35Å R-factor: 0.183 R-free: 0.231

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

Date:

12-May-05 Release date: 29-Nov-05

Protein chain

P0A5I4  (KGUA_MYCTU) -  Guanylate kinase

Seq: 208 a.a.

Struc: 182 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.4.8 - Guanylate kinase.
• Reaction: ATP + GMP = ADP + GDP

ATP + GMP (Bound ligand (Het Group name = 5GP) corresponds exactly) = ADP + GDP

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: growth (3 terms)
• Biochemical function: nucleotide binding (10 terms)

reference

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.

ABSTRACT

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.