title: The X-ray structure of the N-terminal domain of PILB from Neisseria meningitidis reveals a thioredoxin-fold.
abstract: The secreted form of the PilB protein was recently shown to be bound to the outer membrane of Neisseria gonorrhoeae and proposed to be involved in survival of the pathogen to the host's oxidative burst. PilB is composed of three domains. The central and the C-terminal domains display methionine sulfoxide reductase (Msr) A and B activities respectively, i.e. the ability to reduce specifically the S and the R enantiomers of the sulfoxide function of the methionine sulfoxides, which are easily formed upon oxidation of methionine residues. The N-terminal domain of PilB (Dom1(PILB)) of N.meningitidis, which possesses a CXXC motif, was recently shown to recycle the oxidized forms of the PilB Msr domains in vitro, as the Escherichia coli thioredoxin (Trx) 1 does. The X-ray structure of Dom1(PILB) of N.meningitidis determined here shows a Trx-fold, in agreement with the biochemical properties of Dom1(PILB). However, substantial structural differences with E.coli Trx1 exist. Dom1(PILB) displays more structural homologies with the periplasmic disulfide oxidoreductases involved in cytochrome maturation pathways in bacteria. The active site of the reduced form of Dom1(PILB) reveals a high level of stabilization of the N-terminal catalytic cysteine residue and a hydrophobic environment of the C-terminal recycling cysteine in the CXXC motif, consistent with the pK(app) values measured for Cys67 (<6) and Cys70 (9.3), respectively. Compared to cytochrome maturation disulfide oxidoreductases and to Trx1, one edge of the active site is covered by four additional residues (99)FLHE(102). The putative role of the resulting protuberance is discussed in relation to the disulfide reductase properties of Dom1(PILB).
authors.affiliation: LCM3B, Equipe Biocristallographie, UMR 7036 CNRS-UHP, Faculté des Sciences et Techniques, BP 239, 54506 Vandoeuvre, France.
authors.forename: Fanomezana M
authors.initials: FM
authors.lastname: Ranaivoson
authors.forename: Brice
authors.initials: B
authors.lastname: Kauffmann
authors.forename: Fabrice
authors.initials: F
authors.lastname: Neiers
authors.forename: Junzhu
authors.initials: J
authors.lastname: Wu
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boschi-Muller
authors.forename: Santosh
authors.initials: S
authors.lastname: Panjikar
authors.forename: André
authors.initials: A
authors.lastname: Aubry
authors.forename: Guy
authors.initials: G
authors.lastname: Branlant
authors.forename: Frédérique
authors.initials: F
authors.lastname: Favier
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D008715:Methionine / Q000737:chemistry; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D013879:Thioredoxins; D008715:Methionine; D010088:Oxidoreductases; C068255:pilB protein, Bacteria; D003545:Cysteine