PDBsum entry: 1lu4

Oxidoreductase

PDB id: 1lu4

Contents

Protein chain

134 a.a. *

Waters ×321

* Residue conservation analysis

PDB id:

1lu4

Name:

Oxidoreductase

Title:

1.1 angstrom resolution crystal structure of a secreted mycobacterium tuberculosis disulfide oxidoreductase homologous to e. Coli dsbe: implications for functions

Structure:

Soluble secreted antigen mpt53. Chain: a. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: rv2878c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.12Å R-factor: 0.153 R-free: 0.216

Authors:

C.W.Goulding,M.I.Apostol,S.Gleiter,A.Parseghian,J.Bardwell, M.Gennaro,D.Eisenberg,Tb Structural Genomics Consortium (Tbsgc)

Key ref:

C.W.Goulding et al. (2004). Gram-positive DsbE proteins function differently from Gram-negative DsbE homologs. A structure to function analysis of DsbE from Mycobacterium tuberculosis. J Biol Chem, 279, 3516-3524. PubMed id: 14597624 DOI: 10.1074/jbc.M311833200

Date:

21-May-02 Release date: 14-Oct-03

Protein chain

P0A618  (MPT53_MYCTU) -  Soluble secreted antigen MPT53

Seq: 173 a.a.

Struc: 134 a.a.

 Gene Ontology (GO) functional annotation 

• Biological process: cell redox homeostasis (1 term)
• Biochemical function: oxidoreductase activity (1 term)

DOI no: 10.1074/jbc.M311833200

J Biol Chem 279:3516-3524 (2004)

PubMed id: 14597624

Gram-positive DsbE proteins function differently from Gram-negative DsbE homologs. A structure to function analysis of DsbE from Mycobacterium tuberculosis.

C.W.Goulding, M.I.Apostol, S.Gleiter, A.Parseghian, J.Bardwell, M.Gennaro, D.Eisenberg.

ABSTRACT

Mycobacterium tuberculosis, a Gram-positive bacterium, encodes a secreted Dsb-like protein annotated as Mtb DsbE (Rv2878c, also known as MPT53). Because Dsb proteins in Escherichia coli and other bacteria seem to catalyze proper folding during protein secretion and because folding of secreted proteins is thought to be coupled to disulfide oxidoreduction, the function of Mtb DsbE may be to ensure that secreted proteins are in their correctly folded states. We have determined the crystal structure of Mtb DsbE to 1.1 A resolution, which reveals a thioredoxin-like domain with a typical CXXC active site. These cysteines are in their reduced state. Biochemical characterization of Mtb DsbE reveals that this disulfide oxidoreductase is an oxidant, unlike Gram-negative bacteria DsbE proteins, which have been shown to be weak reductants. In addition, the pK(a) value of the active site, solvent-exposed cysteine is approximately 2 pH units lower than that of Gram-negative DsbE homologs. Finally, the reduced form of Mtb DsbE is more stable than the oxidized form, and Mtb DsbE is able to oxidatively fold hirudin. Structural and biochemical analysis implies that Mtb DsbE functions differently from Gram-negative DsbE homologs, and we discuss its possible functional role in the bacterium.

Selected figure(s)

Figure 3.
FIG. 3. Ribbon diagrams of Mtb DsbE and two of the proteins with similar structures. a-c, ribbon diagrams of the structures with the active site cysteines indicated with an arrow. These images were generated using RIBBONS. a, Mtb DsbE; b, B. japonicum DsbE; c, B. japonicum TlpA. It should be noted that all three structures have similar topology, although in Mtb DsbE the active site is in its reduced form, whereas in B. japonicum DsbE and B. japonicum TlpA the active sites are in their oxidized form.

Figure 5.
FIG. 5. Molecular surface representation of monomeric and active site of Mtb DsbE and B. japonicum DsbE. a, illustration of the transparent molecular surface of Mtb DsbE with the ribbon diagram of the structure in orange. b, illustration of the transparent molecular surface of B. japonicum DsbE with the ribbon diagram of the structure in purple. The potential protein interaction groove is indicated. Helix [3] is labeled in both structures. The figure shows that there is no potential protein interaction groove seen in the Mtb DsbE structure as compared with the B. japonicum DsbE structure. c and d, ribbon diagrams of the active sites of Mtb and B. japonicum DsbE structures. The -helices and -strands are shown in cyan and green, respectively. The active site cysteines and amino acid pair atoms are shown in green, red, blue, and yellow, representing carbon, oxygen, nitrogen, and sulfur, respectively. These images were generated using RIBBONS. c, Mtb DsbE; d, B. japonicum DsbE. The hydrogen bond between Trp30 and Glu42 in the Mtb DsbE structure maintains a conformation in which the active cysteines are in their reduced form. In contrast, the hydrogen bond between Asn86 and Glu98 in the B. japonicum DsbE structure maintains a conformation that allows a disulfide bond to form between the active site cysteines.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 3516-3524) copyright 2004.

Figures were selected by an automated process.