1LU4

1.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF A SECRETED MYCOBACTERIUM TUBERCULOSIS DISULFIDE OXIDOREDUCTASE HOMOLOGOUS TO E. COLI DSBE: IMPLICATIONS FOR FUNCTIONS

Summary for 1LU4

• Entry DOI: 10.2210/pdb1lu4/pdb
• Descriptor: SOLUBLE SECRETED ANTIGEN MPT53 (2 entities in total)
• Functional Keywords: thioredoxin-like fold, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, oxidoreductase
• Biological source: Mycobacterium tuberculosis
• Cellular location: Secreted: P0A618
• Total number of polymer chains: 1
• Total formula weight: 14624.24

Authors

Goulding, C.W.,Apostol, M.I.,Gleiter, S.,Parseghian, A.,Bardwell, J.,Gennaro, M.,Eisenberg, D.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2002-05-21, release date: 2003-10-14, Last modification date: 2024-02-14)

Primary citation

Goulding, C.W.,Apostol, M.I.,Gleiter, S.,Parseghian, A.,Bardwell, J.,Gennaro, M.,Eisenberg, D.
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, 2004

PubMed 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.

PubMed: 14597624
DOI: 10.1074/jbc.M311833200

Experimental method

X-RAY DIFFRACTION (1.12 Å)