3moo

Crystal structure of the HmuO, heme oxygenase from Corynebacterium diphtheriae, in complex with azide-bound verdoheme

spinqualitylabelsall models 3moo, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3moo is a 2 chain structure with sequence from Corynebacterium diphtheriae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AZI, SO4, SUC, VEA Related: 1iw0, 1iw1, 1v8x, 2zvu, 1twn, 1twr Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The least understood mechanism during heme degradation by the enzyme heme oxygenase (HO) is the third step of ring opening of verdoheme to biliverdin, a process which maintains iron homeostasis. In response to this mechanistic uncertainty, we launched a combined study of X-ray crystallography and theoretical QM/MM calculations, designed to elucidate the mechanism. The air-sensitive ferrous verdoheme complex of HmuO, a heme oxygenase from Corynebacterium diphtheriae, was crystallized under anaerobic conditions. Spectral analysis of the azide-bound verdoheme-HmuO complex crystals assures that the verdoheme group remains intact during the crystallization and X-ray diffraction measurement. The structure offers the first solid evidence for the presence of a water cluster in the distal pocket of this catalytically critical intermediate. The subsequent QM/MM calculations based on this crystal structure explore the reaction mechanisms starting from the FeOOH-verdoheme and FeHOOH-verdoheme complexes, which mimic, respectively, the O(2)- and H(2)O(2)-supported degradations. In both mechanisms, the rate-determining step is the initial O-O bond breaking step, which is either homolytic (for FeHOOH-verdoheme) or coupled to electron and proton transfers (in FeOOH-verdoheme). Additionally, the calculations indicate that the FeHOOH-verdoheme complex is more reactive than the FeOOH-verdoheme complex in accord with experimental findings. QM energies with embedded MM charges are close to and yield the same conclusions as full QM/MM energies. Finally, the calculations highlight the dominant influence of the distal water cluster which acts as a biocatalyst for the conversion of verdoheme to biliverdin in the two processes, by fixing the departing OH and directing it to the requisite site of attack, and by acting as a proton shuttle and a haven for the highly reactive OH(-) nucleophile. Enzymatic ring-opening mechanism of verdoheme by the heme oxygenase: a combined X-ray crystallography and QM/MM study.,Lai W, Chen H, Matsui T, Omori K, Unno M, Ikeda-Saito M, Shaik S J Am Chem Soc. 2010 Sep 22;132(37):12960-70. PMID:20806922 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heme oxygenase

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