2ZDO

Crystal structure of IsdG-N7A in complex with hemin

Summary for 2ZDO

• Entry DOI: 10.2210/pdb2zdo/pdb
• Related: 1SQE 1XBW 2ZDP
• Descriptor: Heme-degrading monooxygenase isdG, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: ruffling, protein-substrate complex, cytoplasm, heme, iron, metal-binding, monooxygenase, oxidoreductase
• Biological source: Staphylococcus aureus
• Cellular location: Cytoplasm (By similarity): Q7A649
• Total number of polymer chains: 4
• Total formula weight: 53307.73

Authors

Lee, W.C.,Reniere, M.L.,Skaar, E.P.,Murphy, M.E.P. (deposition date: 2007-11-27, release date: 2008-08-19, Last modification date: 2023-11-01)

Primary citation

Lee, W.C.,Reniere, M.L.,Skaar, E.P.,Murphy, M.E.P.
Ruffling of Metalloporphyrins Bound to IsdG and IsdI, Two Heme-degrading Enzymes in Staphylococcus aureus
J.Biol.Chem., 283:30957-30963, 2008

PubMed Abstract: IsdG and IsdI are paralogous proteins that are intracellular components of a complex heme uptake system in Staphylococcus aureus. IsdG and IsdI were shown previously to reductively degrade hemin. Crystal structures of the apoproteins show that these proteins belong to a newly identified heme degradation family distinct from canonical eukaryotic and prokaryotic heme oxygenases. Here we report the crystal structures of an inactive N7A variant of IsdG in complex with Fe(3+)-protoporphyrin IX (IsdG-hemin) and of IsdI in complex with cobalt protoporphyrin IX (IsdI-CoPPIX) to 1.8 A or better resolution. These structures show that the metalloporphyrins are buried into similar deep clefts such that the propionic acids form salt bridges to two Arg residues. His(77) (IsdG) or His(76) (IsdI), a critical residue required for activity, is coordinated to the Fe(3+) or Co(3+) atoms, respectively. The bound porphyrin rings form extensive steric interactions in the binding cleft such that the rings are highly distorted from the plane. This distortion is best described as ruffled and places the beta- and delta-meso carbons proximal to the distal oxygen-binding site. In the IsdG-hemin structure, Fe(3+) is pentacoordinate, and the distal side is occluded by the side chain of Ile(55). However, in the structure of IsdI-CoPPIX, the distal side of the CoPPIX accommodates a chloride ion in a cavity formed through a conformational change in Ile(55). The chloride ion participates in a hydrogen bond to the side chain amide of Asn(6). Together the structures suggest a reaction mechanism in which a reactive peroxide intermediate proceeds with nucleophilic oxidation at the beta- or delta-meso carbon of the hemin.

PubMed: 18713745
DOI: 10.1074/jbc.M709486200

Experimental method

X-RAY DIFFRACTION (1.8 Å)