title: Prostaphopain B structure: a comparison of proregion-mediated and staphostatin-mediated protease inhibition.
abstract: Prostaphopain B is the precursor of staphopain B, a papain-type secreted cysteine protease from the pathogen Staphylococcus aureus. Here, we describe the 2.5 A crystal structure of the proenzyme. Its 21 kDa proregion is organized around a central half-barrel or barrel-sandwich hybrid and occludes primed, but not nonprimed, sites in the active site cleft of the protease. The structure of the mature part of the protease is similar to previously reported staphopain structures, and no distortion of the catalytic residues is apparent at 2.5 A resolution. A comparison of prostaphopain B with the staphopain B-staphostatin B complex shows that the proregion and the inhibitor interact with largely nonoverlapping parts of the protease surface. In a modeled complex of prostaphopain B with staphostatin B, clashes occur both inside and outside the active site cleft, but involve mostly poorly ordered regions of the protein that may be mobile.
authors.affiliation: International Institute of Molecular and Cell Biology, ul. Trojdena 4, 02-109 Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Filipek
authors.forename: Roman
authors.initials: R
authors.lastname: Szczepanowski
authors.forename: Artur
authors.initials: A
authors.lastname: Sabat
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Matthias
authors.initials: M
authors.lastname: Bochtler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry*; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C479136:staphostatin B protein, Staphylococcus aureus; D003546:Cysteine Endopeptidases; C479137:staphopain B protein, Staphylococcus aureus