Revisiting catalytic His and Glu residues in coproporphyrin ferrochelatase - unexpected activities of active site variants.
LC-MS
enzyme activity
ferrochelatase
prokaryotic heme biosynthesis
resonance Raman spectroscopy
site-directed mutagenesis
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
23 Feb 2024
23 Feb 2024
Historique:
revised:
17
01
2024
received:
13
12
2023
accepted:
13
02
2024
medline:
23
2
2024
pubmed:
23
2
2024
entrez:
23
2
2024
Statut:
aheadofprint
Résumé
The identification of the coproporphyrin-dependent heme biosynthetic pathway, which is used almost exclusively by monoderm bacteria in 2015 by Dailey et al. triggered studies aimed at investigating the enzymes involved in this pathway that were originally assigned to the protoporphyrin-dependent heme biosynthetic pathway. Here, we revisit the active site of coproporphyrin ferrochelatase by a biophysical and biochemical investigation using the physiological substrate coproporphyrin III, which in contrast to the previously used substrate protoporphyrin IX has four propionate substituents and no vinyl groups. In particular, we have compared the reactivity of wild-type coproporphyrin ferrochelatase from the firmicute Listeria monocytogenes with those of variants, namely, His182Ala (H182A) and Glu263Gln (E263Q), involving two key active site residues. Interestingly, both variants are active only toward the physiological substrate coproporphyrin III but inactive toward protoporphyrin IX. In addition, E263 exchange impairs the final oxidation step from ferrous coproheme to ferric coproheme. The characteristics of the active site in the context of the residues involved and the substrate binding properties are discussed here using structural and functional means, providing a further contribution to the deciphering of this enigmatic reaction mechanism.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund
ID : P33544
Organisme : Austrian Science Fund
ID : P36967
Organisme : Austrian Science Fund
ID : W1224
Organisme : Fondazione Cassa di Risparmio di Firenze
ID : 2020.1397
Organisme : EQ-BOKU VIBT GmbH
Organisme : BOKU Core Facility Mass Spectrometry
Organisme : MUR-Italy
ID : CUP B97G22000740001 - DICUS 2.0
Organisme : MUR-Italy
ID : CUP B96C1700020008
Informations de copyright
© 2024 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Dailey HA, Gerdes S, Dailey TA, Burch JS & Phillips JD (2015) Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. Proc Natl Acad Sci USA 112, 2210-2215.
Dailey HA, Dailey TA, Gerdes S, Jahn D, Jahn M, O'Brian MR & Warren MJ (2017) Prokaryotic Heme biosynthesis: multiple pathways to a common essential product. Microbiol Mol Biol Rev 81, e00048-16.
Layer G (2021) Heme biosynthesis in prokaryotes. Biochim Biophys Acta Mol Cell Res 1868, 118861.
Dailey HA, Dailey TA, Wu CK, Medlock AE, Wang KF, Rose JP & Wang BC (2000) Ferrochelatase at the millennium: structures, mechanisms and [2Fe-2S] clusters. Cell Mol Life Sci 57, 1909-1926.
Hofbauer S, Helm J, Obinger C, Djinović-Carugo K & Furtmüller PG (2020) Crystal structures and calorimetry reveal catalytically relevant binding mode of coproporphyrin and coproheme in coproporphyrin ferrochelatase. FEBS J 287, 2779-2796.
Gabler T, Sebastiani F, Helm J, Dali A, Obinger C, Furtmüller PG, Smulevich G & Hofbauer S (2022) Substrate specificity and complex stability of coproporphyrin ferrochelatase is governed by hydrogen-bonding interactions of the four propionate groups. FEBS J 289, 1680-1699.
Dali A, Gabler T, Sebastiani F, Destinger A, Furtmüller PG, Pfanzagl V, Becucci M, Smulevich G & Hofbauer S (2023) Active site architecture of coproporphyrin ferrochelatase with its physiological substrate coproporphyrin III: propionate interactions and porphyrin core deformation. Protein Sci 32, e4534.
Weerth RS, Medlock AE & Dailey HA (2021) Ironing out the distribution of [2Fe-2S] motifs in ferrochelatases. J Biol Chem 297, 101017.
Shepherd M, Dailey TA & Dailey HA (2006) A new class of [2Fe-2S]-cluster-containing protoporphyrin (IX) ferrochelatases. Biochem J 397, 47-52.
Pfanzagl V, Holcik L, Maresch D, Gorgone G, Michlits H, Furtmüller PG & Hofbauer S (2018) Coproheme decarboxylases - phylogenetic prediction versus biochemical experiments. Arch Biochem Biophys 640, 27-36.
Dailey HA & Medlock AE (2022) A primer on heme biosynthesis. Biol Chem 403, 985-1003.
Hansson MD, Karlberg T, Rahardja MA, Al-Karadaghi S & Hansson M (2007) Amino acid residues His183 and Glu264 in Bacillus subtilis ferrochelatase direct and facilitate the insertion of metal ion into protoporphyrin IX. Biochemistry 46, 87-94.
Wang Y & Shen Y (2013) Is it possible for Fe2+ to approach protoporphyrin IX from the side of Tyr-13 in Bacillus subtilis ferrochelatase? An answer from QM/MM study. J Mol Model 19, 963-971.
Hansson MD, Karlberg T, Söderberg CA, Rajan S, Warren MJ, Al-Karadaghi S, Rigby SE & Hansson M (2011) Bacterial ferrochelatase turns human: Tyr13 determines the apparent metal specificity of Bacillus subtilis ferrochelatase. J Biol Inorg Chem 16, 235-242.
Karlberg T, Hansson MD, Yengo RK, Johansson R, Thorvaldsen HO, Ferreira GC, Hansson M & Al-Karadaghi S (2008) Porphyrin binding and distortion and substrate specificity in the ferrochelatase reaction: the role of active site residues. J Mol Biol 378, 1074-1083.
Franco R, Ma JG, Lu Y, Ferreira GC & Shelnutt JA (2000) Porphyrin interactions with wild-type and mutant mouse ferrochelatase. Biochemistry 39, 2517-2529.
Hoggins M, Dailey HA, Hunter CN & Reid JD (2007) Direct measurement of metal ion chelation in the active site of human ferrochelatase. Biochemistry 46, 8121-8127.
Medlock A, Swartz L, Dailey TA, Dailey HA & Lanzilotta WN (2007) Substrate interactions with human ferrochelatase. Proc Natl Acad Sci USA 104, 1789-1793.
Karlberg T, Lecerof D, Gora M, Silvegren G, Labbe-Bois R, Hansson M & Al-Karadaghi S (2002) Metal binding to Saccharomyces cerevisiae ferrochelatase. Biochemistry 41, 13499-13506.
Hunter GA, Sampson MP & Ferreira GC (2008) Metal ion substrate inhibition of ferrochelatase. J Biol Chem 283, 23685-23691.
Gora M, Grzybowska E, Rytka J & Labbe-Bois R (1996) Probing the active-site residues in Saccharomyces cerevisiae ferrochelatase by directed mutagenesis. In vivo and in vitro analyses. J Biol Chem 271, 11810-11816.
Sellers VM, Wu CK, Dailey TA & Dailey HA (2001) Human ferrochelatase: characterization of substrate-iron binding and proton-abstracting residues. Biochemistry 40, 9821-9827.
Medlock AE, Dailey TA, Ross TA, Dailey HA & Lanzilotta WN (2007) A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase. J Mol Biol 373, 1006-1016.
Medlock AE, Najahi-Missaoui W, Shiferaw MT, Albetel AN, Lanzilotta WN & Dailey HA (2021) Insight into the function of active site residues in the catalytic mechanism of human ferrochelatase. Biochem J 478, 3239-3252.
Celis AI, Gauss GH, Streit BR, Shisler K, Moraski GC, Rodgers KR, Lukat-Rodgers GS, Peters JW & DuBois JL (2017) Structure-based mechanism for oxidative decarboxylation reactions mediated by amino acids and Heme propionates in Coproheme decarboxylase (HemQ). J Am Chem Soc 139, 1900-1911.
Milazzo L, Gabler T, Pühringer D, Jandova Z, Maresch D, Michlits H, Pfanzagl V, Djinović-Carugo K, Oostenbrink C, Furtmüller PG et al. (2019) Redox cofactor rotates during its stepwise decarboxylation: molecular mechanism of conversion of Coproheme to Heme. ACS Catal 9, 6766-6782.
Michlits H, Lier B, Pfanzagl V, Djinović-Carugo K, Furtmüller PG, Oostenbrink C, Obinger C & Hofbauer S (2020) Actinobacterial coproheme decarboxylases use histidine as distal base to promote compound I formation. ACS Catal 10, 5405-5413.
Sebastiani F, Michlits H, Lier B, Becucci M, Furtmüller PG, Oostenbrink C, Obinger C, Hofbauer S & Smulevich G (2021) Reaction intermediate rotation during the decarboxylation of coproheme to heme b in C. Diphtheriae. Biophys J 120, 3600-3614.
Gabler T, Dali A, Sebastiani F, Furtmüller PG, Becucci M, Hofbauer S & Smulevich G (2023) Iron insertion into coproporphyrin III-ferrochelatase complex: evidence for an intermediate distorted catalytic species. Protein Sci 32, e4788.
Dailey HA & Gerdes S (2015) HemQ: An iron-coproporphyrin oxidative decarboxylase for protoheme synthesis in Firmicutes and Actinobacteria. Arch Biochem Biophys 574, 27-35.
Hunter GA & Ferreira GC (2022) Metal ion coordination sites in ferrochelatase. Coord Chem Rev 460, 214464.
Wu CK, Dailey HA, Rose JP, Burden A, Sellers VM & Wang BC (2001) The 2.0 a structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Biol 8, 156-160.
Asuru AP, An M & Busenlehner LS (2012) Dissection of porphyrin-induced conformational dynamics in the heme biosynthesis enzyme ferrochelatase. Biochemistry 51, 7116-7127.
Wu J, Wen S, Zhou Y, Chao H & Shen Y (2016) Human Ferrochelatase: insights for the mechanism of ferrous iron approaching Protoporphyrin IX by QM/MM and QTCP free energy studies. J Chem Inf Model 56, 2421-2433.
Lecerof D, Fodje M, Hansson A, Hansson M & Al-Karadaghi S (2000) Structural and mechanistic basis of porphyrin metallation by ferrochelatase. J Mol Biol 297, 221-232.
Franco R, Al-Karadaghi S & Ferreira GC (2011) Resonance Raman spectroscopic examination of Ferrochelatase-induced porphyrin distortion. J Porphyr Phthalocyanines 15, 357-363.
Hofbauer S, Gysel K, Bellei M, Hagmüller A, Schaffner I, Mlynek G, Kostan J, Pirker KF, Daims H, Furtmüller PG et al. (2014) Manipulating conserved heme cavity residues of chlorite dismutase: effect on structure, redox chemistry, and reactivity. Biochemistry 53, 77-89.