Harderoporphyrinogen-I is metabolized by avian hemolysate preparations of coproporphyrinogen oxidase to give a trivinylic product; this unprecedented 'overmetabolism' of the porphyrinogen substrate provides strong support for a proposed model of the active site of this poorly understood enzyme.
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http://dx.doi.org/10.1016/s0960-894x(02)00097-5 | DOI Listing |
Angew Chem Int Ed Engl
July 2021
Anorganisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120, Heidelberg, Germany.
The present work describes the reaction of triplet dioxygen with the porphyrinogenic calix[4]pyrrolato aluminates to alkylperoxido aluminates in high selectivity. Multiconfigurational quantum chemical computations disclose the mechanism for this spin-forbidden process. Despite a negligible spin-orbit coupling constant, the intersystem crossing (ISC) is facilitated by singlet and triplet state degeneracy and spin-vibronic coupling.
View Article and Find Full Text PDFBiochem J
March 2021
Department of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Hydroxymethylbilane synthase (HMBS), which is involved in the heme biosynthesis pathway, has a dipyrromethane cofactor and combines four porphobilinogen (PBG) molecules to form a linear tetrapyrrole, hydroxymethylbilane. Enzyme kinetic study of human HMBS using a PBG-derivative, 2-iodoporphobilinogen (2-I-PBG), exhibited noncompetitive inhibition with the inhibition constant being 5.4 ± 0.
View Article and Find Full Text PDFBr J Cancer
October 2019
Department of Renal Medicine, Flinders Medical Centre, Flinders University, Bedford Park, SA, 5042, Australia.
Photodynamic diagnosis and therapy have emerged as a promising tool in oncology. Using the visible fluorescence from photosensitisers excited by light, clinicians can both identify and treat tumour cells in situ. Protoporphyrin IX, produced in the penultimate step of the haem synthesis pathway, is a naturally occurring photosensitiser that visibly fluoresces when exposed to light.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
September 2018
Protein Stability and Inherited Disease Laboratory, CIC bioGUNE, Derio, Bizkaia 48160, Spain. Electronic address:
Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time. The four intermediate complexes of the enzyme have been biochemically validated and they can be isolated but they have never been structurally characterized other than the apo- and holo-enzyme bound to the cofactor.
View Article and Find Full Text PDFStructure
April 2018
EMBL-EBI, Wellcome Genome Campus, Hinxton CB10 1SD, UK.
There are numerous applications that use the structures of protein-ligand complexes from the PDB, such as 3D pharmacophore identification, virtual screening, and fragment-based drug design. The structures underlying these applications are potentially much more informative if they contain biologically relevant bound ligands, with high similarity to the cognate ligands. We present a study of ligand-enzyme complexes that compares the similarity of bound and cognate ligands, enabling the best matches to be identified.
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