title: In vivo heme scavenging by Staphylococcus aureus IsdC and IsdE proteins.
abstract: We report the first characterization of the in vivo porphyrin scavenging abilities of two components of a newly discovered heme scavenging system involving iron-regulated surface determinant (Isd) proteins. These proteins are present within the cell envelope of the Gram-positive human pathogen Staphylococcus aureus. IsdC and IsdE, when expressed heterologously in Escherichia coli, efficiently scavenged intracellular heme and resulted in de novo heme synthesis in excess of 100-fold above background. Magnetic circular dichroism analyses showed that the heme-binding properties of the two proteins differ significantly from one another. IsdC bound almost exclusively free-base protoporphyrin IX, whereas the IsdE protein was associated with low spin Fe(III) and Fe(II) heme. These properties provide important insight into the possible mechanisms of iron scavenging from bound heme by Isd proteins.
authors.affiliation: Department of Chemistry, University of Western Ontario, London, Ont., Canada N6A 5B7.
authors.forename: John
authors.initials: J
authors.lastname: Mack
authors.forename: Christie
authors.initials: C
authors.lastname: Vermeiren
authors.forename: David E
authors.initials: DE
authors.lastname: Heinrichs
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stillman
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism / Q000379:methods; D006418:Heme / Q000737:chemistry* / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011166:Porphyrins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; C488727:IsdC protein, Staphylococcus aureus; C488728:IsdE protein, Staphylococcus aureus; D011166:Porphyrins; D006418:Heme