The conserved active-site loop residues of ferrochelatase induce porphyrin conformational changes necessary for catalysis

Biochemistry
Zhen ShiG C Ferreira

Abstract

Binding of porphyrin to murine ferrochelatase, the terminal enzyme of the heme biosynthetic pathway, is investigated by employing a set of variants harboring mutations in a putative porphyrin-binding loop. Using resonance Raman (RR) spectroscopy, the structural properties of the ferrochelatase-bound porphyrins are examined, especially with respect to the porphyrin deformation occurring in the environment of the active site. This deformation is thought to be a key step in the enzymatic insertion of ferrous iron into the porphyrin ring to make heme. Our previous RR spectroscopic studies of binding of porphyrin to murine ferrochelatase led us to propose that the wild-type enzyme induces porphyrin distortion even in the absence of the metal ion substrate. Here, we broaden this view by presenting evidence that the degree of a specific nonplanar porphyrin deformation contributes to the catalytic efficiency of ferrochelatase and its variants. The results also suggest that the conserved Trp256 (murine ferrochelatase numbering) is partially responsible for the observed porphyrin deformation. Binding of porphyrin to the ferrochelatase variants causes a decrease in the intensity of RR out-of-plane vibrational mode gamma(15), a saddling-li...Continue Reading

References

Aug 17, 1990·Science·A G Cochran, P G Schultz
Oct 1, 1985·Analytical Biochemistry·P K SmithD C Klenk
Apr 1, 1995·Journal of Bioenergetics and Biomembranes·G C FerreiraB H Huynh
Dec 3, 1999·The International Journal of Biochemistry & Cell Biology·G C Ferreira
Mar 8, 2000·Biochemistry·R FrancoJ A Shelnutt
Mar 8, 2000·Journal of Molecular Biology·D LecerofS Al-Karadaghi
Nov 13, 2002·Biochemistry·Tobias KarlbergSalam Al-Karadaghi
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jun YinPeter G Schultz
Feb 18, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Emma Sigfridsson, Ulf Ryde
May 23, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·David LecerofSalam Al-Karadaghi
Feb 26, 2004·The Journal of Biological Chemistry·Zhen Shi, Gloria C Ferreira
Dec 17, 2004·Journal of the American Chemical Society·Swarnalatha VenkateshraoThomas G Spiro

❮ Previous
Next ❯

Citations

Jun 24, 2010·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Beate RöderMathias O Senge
Jan 31, 2007·Proceedings of the National Academy of Sciences of the United States of America·Amy MedlockWilliam N Lanzilotta
Jul 22, 2011·Journal of Porphyrins and Phthalocyanines·Ricardo FrancoGloria C Ferreira
Aug 20, 2011·Journal of Porphyrins and Phthalocyanines·Gregory A HunterGloria C Ferreira
Dec 24, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Ariel E Schuelke-SanchezMatthew D Liptak
Jun 24, 2006·The Biochemical Journal·Zhen Shi, Gloria C Ferreira
Sep 17, 2020·The Journal of Physical Chemistry. a·Alexandr GorskiJacek Waluk

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.