553-12-8Relevant academic research and scientific papers
A point mutation of valine-311 to methionine in Bacillus subtilis protoporphyrinogen oxidase does not greatly increase resistance to the diphenyl ether herbicide oxyfluorfen
Jeong, Eunjoo,Houn, Thavrak,Kuk, Yongin,Kim, Eun-Seon,Chandru, Hema Kumar,Baik, Myunggi,Back, Kyoungwhan,Guh, Ja-Ock,Han, Oksoo
, p. 389 - 397 (2003)
In an effort to asses the effect of Val311Met point mutation of Bacillus subtilis protoporphyrinogen oxidase on the resistance to diphenyl ether herbicides, a Val311Met point mutant of B. subtilis protoporphyrinogen oxidase was prepared, heterologously expressed in Escherichia coli, and the purified recombinant Val311Met mutant protoporphyrinogen oxidase was kinetically characterized. The mutant protoporphyrinogen oxidase showed very similar kinetic patterns to wild type protoporphyrinogen oxidase, with slightly decreased activity dependent on pH and the concentrations of NaCl, Tween 20, and imidazole. When oxyfluorfen was used as a competitive inhibitor, the Val311Met mutant protoporphyrinogen oxidase showed an increased inhibition constant about 1.5 times that of wild type protoporphyrinogen oxidase. The marginal increase of the inhibition constant indicates that the Val311Met point mutation in B. subtilis protoporphyrinogen oxidase may not be an important determinant in the mechanism that protects protoporphyrinogen oxidase against diphenyl ether herbicides.
Self-Sensitized Photooxidation of Protoporphyrin IX Derivatives in Aqueous Surfactant Solutions: Product and Mechanistic Studies
Cox, G. Sidney,Krieg, Marianne,Whitten, David G.
, p. 6930 - 6937 (1982)
The photooxidation of protoporphyrin IX and its dimethyl ester has been investigated in several aqueous surfactant media including neutral micelles (Brij 35) and vesicles (dipalmitoylphosphatidylcholine) and charged micelles (SDS and DTAB).The results obtained indicate that while the same products are formed in these media as in homogeneous organic solvents such as methylene chloride, the product distributions are quite different.At least two major reaction paths are indicated.The first involves singlet oxygen generation and attack on ground-state porphyrins.This path can be shown by studies with H2O vs.D2O and the use of the aqueous phase quencher N3- to consist of two components, an intramicellar path and an intermicellar reaction.The second path appears most likely to involve electron transfer from excited porphyrin to generate superoxide and porphyrin ?-cation.This path appears to be exclusively intramicellar and is much more prominent in the organized media than in homogeneous solution.Quenching of 1O2* by azide appears to enhance the "superoxide-derived" products in SDS and Brij 35 supporting recent studies indicating that azide quenching occurs at least in part of electron transfer.
Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease
Wang, Nan,Jin, Xin,Guo, Dongbo,Tong, Gangsheng,Zhu, Xinyuan
, p. 461 - 474 (2017)
Iron accumulation in substantia nigra pars compacta (SNpc) has been proved to be a prominent pathophysiological feature of Parkinson’s diseases (PD), which can induce the death of dopaminergic (DA) neurons, up-regulation of reactive oxygen species (ROS), and further loss of motor control. In recent years, iron chelation therapy has been demonstrated to be an effective treatment for PD, which has shown significant improvements in clinical trials. However, the current iron chelators are suboptimal due to their short circulation time, side effects, and lack of proper protection from chelation with ions in blood circulation. In this work, we designed and constructed iron chelation therapeutic nanoparticles protected by a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) to delay the saturation of iron chelators in blood circulation and prolong the in vivo lifetime, with HIV-1 trans-activating transcriptor (TAT) served as a shuttle to enhance the blood-brain barrier (BBB) permeability. We explored and investigated whether the Parkinsonian neurodegeneration and the corresponding symptoms in behaviors and physiologies could be prevented or reversed both in vitro and in vivo. The results demonstrated that iron chelator loaded therapeutic nanoparticles could reverse functional deficits in Parkinsonian mice not only physiologically but also behaviorally. On the contrary, both untreated PD mice and non-TAT anchored nanoparticle treated PD mice showed similar loss in DA neurons and difficulties in behaviors. Therefore, with protection of zwitterionic polymer and prolonged in vivo lifetime, iron chelator loaded nanoparticles with delayed saturation provide a PD phenotype reversion therapy and significantly improve the living quality of the Parkinsonian mice.
On the Nature of 'Haematoporphyrin Derivative'
Bonnett, Raymond,Ridge, Richard J.,Scourides, Panayiotis A.,Berenbaum, Morris C.
, p. 3135 - 3140 (1981)
The components of haematoporphyrin derivative ( a preparation used as a photosensitiser in clinical applications, and made by treating haematoporphyrin with sulphuric acid-acetic acid) have been separated by preparative h.p.l.c. and identified by comparison with authentic porphyrincarboxylic acids.The composition of the mixture is somewhat variable but the main components are O,O'-diacetylhaematoporphyrin (6) and O-acetylhaematoporphyrin (2)/(3) with smaller amounts of the 8(3)-(1-acetoxyethyl)-3(8)-vinyldeuteroporphyrin isomers (7) and (8) and the corresponding alcohols (4) and (5).
Quantitative structural insight into human variegate porphyria disease
Wang, Baifan,Wen, Xin,Qin, Xiaohong,Wang, Zhifang,Tan, Ying,Shen, Yuequan,Xi, Zhen
, p. 11731 - 11740 (2013)
Defects in the human protoporphyrinogen oxidase (hPPO) gene, resulting in ～ 50% decreased activity of hPPO, is responsible for the dominantly inherited disorder variegate porphyria (VP). To understand the molecular mechanism of VP, we employed the sitedirected mutagenesis, biochemical assays, structural biology, and molecular dynamics simulation studies to investigate VP-causing hPPO mutants. We report here the crystal structures of R59Q and R59G mutants in complex with acifluorfen at a resolution of 2.6 and 2.8 A. The r.m.s.d. of the Cα atoms of the active site structure of R59G and R59Q with respect to the wild-type was 0.20 and 0.15 A, respectively. However, these highly similar static crystal structures of mutants with the wild-type could not quantitatively explain the observed large differences in their enzymatic activity. To understand how the hPPO mutations affect their catalytic activities, we combined molecular dynamics simulation and statistical analysis to quantitatively understand the molecular mechanism of VP-causing mutants. We have found that the probability of the privileged conformations of hPPO can be correlated very well with the kcat/Km of PPO (correlation coefficient, R2 > 0.9), and the catalytic activity of 44 clinically reported VP-causing mutants can be accurately predicted. These results indicated that the VP-causing mutation affect the catalytic activity of hPPO by affecting the ability of hPPO to sample the privileged conformations. The current work, together with our previous crystal structure study on the wild-type hPPO, provided the quantitative structural insight into human variegate porphyria disease.
Haematoporphyrin Derivative
Bonnett, Raymond,Ridge, Richard J.,Scourides, Panayiotis A.,Berenbaum, Morris C.
, p. 1198 - 1199 (1980)
Components of 'haematoporphyrin derivative,' a photosensitiser employed in clinical studies, have been separated as the free acids by reverse-phase high pressure liquid chromatography, and identified, the major components being O,O'-diacetylhaematoporphyrin and O-acetylhaematoporphyrin.
ROMP polymer supported manganese porphyrins: Influence of C[dbnd]C bonds along polymer chains on catalytic behavior in oxidation of low concentration Fe2+
Li, Fanfan,Wang, Xuan,Zhang, Yanwu,Zhao, Huanhuan
, (2020/02/22)
One unsaturated polymer support was prepared through ring opening metathesis polymerization (ROMP) of norbornene-2,3-dip-toluene sulfonate initiated by Grubbs 2nd initiator and manganese porphyrins were immobilized on polymer through transesterification reaction. To investigate the effect of C[dbnd]C bonds along polymer chains on the catalytic behavior, the obtained polymer supported catalyst (P-PPIXMnCl) was applied in oxidation of low concentration Fe2+ to mimic catalytic behavior of Ceruloplasmin. In the presence of P-PPIXMnCl, the conversion of Fe2+ reaches to 91.92% and 96.46% at 10 °C and 37.5 °C (body temperature), respectively. Compared to manganese porphyrins, P-PPIXMnCl can dramatically increase oxidation rate of Fe2+ and the catalytic kinetic shows that the oxidation reaction changes from second-order to third-order. Upon hydrogenation of ROMP polymer, the oxidation reaction still conforms to the second-order kinetics. Density functional theory (DFT) calculation shows that the C[dbnd]C bonds along polymer chains play an important role in the coordination with Fe2+ in the catalytic microenvironment. The real time morphology of supported catalysts in aqueous environment characterized by Cryo-TEM indicates that hydrogenation can shrink the morphology of polymer-water skeleton. The catalyst could be recycled six times without any significant loss in activity. The liner heterogeneous catalyst is expected to be used as drugs for treating excessive iron accumulation in the human body.
Handling heme: The mechanisms underlying the movement of heme within and between cells
Donegan, Rebecca K.,Moore, Courtney M.,Hanna, David A.,Reddi, Amit R.
, p. 88 - 100 (2018/08/21)
Heme is an essential cofactor and signaling molecule required for virtually all aerobic life. However, excess heme is cytotoxic. Therefore, heme must be safely transported and trafficked from the site of synthesis in the mitochondria or uptake at the cell surface, to hemoproteins in most subcellular compartments. While heme synthesis and degradation are relatively well characterized, little is known about how heme is trafficked and transported throughout the cell. Herein, we review eukaryotic heme transport, trafficking, and mobilization, with a focus on factors that regulate bioavailable heme. We also highlight the role of gasotransmitters and small molecules in heme mobilization and bioavailability, and heme trafficking at the host-pathogen interface.
Revisiting the Mechanism of the Anaerobic Coproporphyrinogen III Oxidase HemN
Ji, Xinjian,Mo, Tianlu,Liu, Wan-Qiu,Ding, Wei,Deng, Zixin,Zhang, Qi
supporting information, p. 6235 - 6238 (2019/04/04)
HemN is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, an intermediate in heme biosynthesis. HemN binds two SAM molecules in the active site, but how these two SAMs are utilized for the sequential decarboxylation of the two propionate groups of coproporphyrinogen III remains largely elusive. Provided here is evidence showing that in HemN catalysis a SAM serves as a hydrogen relay which mediates a radical-based hydrogen transfer from the propionate to the 5′-deoxyadenosyl (dAdo) radical generated from another SAM in the active site. Also observed was an unexpected shunt product resulting from trapping of the SAM-based methylene radical by the vinyl moiety of the mono-decarboxylated intermediate, harderoporphyrinogen. These results suggest a major revision of the HemN mechanism and reveal a new paradigm of the radical-mediated hydrogen transfer in radical SAM enzymology.
TARGETED ANTIMICROBIAL PHOTODYNAMIC THERAPY
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Paragraph 0177, (2019/10/29)
The present application relates generally to a method and a composition matter that provides a rapid and potent antimicrobial photodynamic inactivation (aPDI) of pathogenic bacteria that express high-affinity cell-surface hemin receptors (CSHRs) using Ga(III)-protoporphyrins IX (GaPpIX or Ga-PpIX). The invention provides an effective treatment option for infections of skin or body cavities that are accessible to visible-light irradiation, such as a handheld LED array emitting visible light (405 nm), especially for infections caused by Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), pathogenic staphylococci, Streptococcus mutans, S. pneumoniae, S. pyogenes, streptococci, corynebacteria, mycobacteria, and Bacillus anthracis.
