Simon Labbé's work on iron and copper homeostasis

Iron and copper have a wealth of functions in biological systems,which makes them essential micronutrients for all living organisms.Defects in iron and copper homeostasis are directly responsible for diseases,and have been linked to impaired development,metabolic syndromes and fungal virulence.Consequently,it is crucial to gain a comprehensive understanding of the molecular bases of iron-and copper-dependent proteins in living systems.Simon Labbémaintains parallel programs on iron and copper homeostasis using the fission yeast Schizosaccharomyces pombe(Schiz.pombe) as a model system.The study of fission yeast transition-metal metabolism has been successful,not only in discerning the genes and pathways functioning in Schiz.pombe,but also the genes and pathways that are active in mammalian systems and for other fungi.

Enzymatic Characterisation of Lignin Peroxidase from Luffa aegyptiaca Fruit Juice

Luffa aegyptiaca fruit has been assayed for the presence of lignin peroxidase activity using veratryl alcohol as the substrate. The fruit juice contained activity of 3.14 U/ml which was much higher than 0.075 U/ml reported in the culture filtrate of Phanarochaete chrysosporium ATCC-24725. The Km value of the lignin peroxidase using veratryl alcohol as the variable substrate in 50mM phosphate buffer pH 2.5 at 25°C was found to be 50 μM respectively. The pH and temperature optima of the lignin peroxidase were 2.4 and 22°C, respectively. The present article reports viable method to explore rich sources of lignin peroxidase from plants which can be used as a mediator in oxidative organic transformations within green chemistry domain ensuring ecofriendly synthesis of bioorganic molecules of pharmaceutical value.

x-ray Crystal Structure of a Dinuclear Zinc(Ⅱ) Complex with Unusual Two Monodentate O-coordination of Carboxylate Group of Isonicotinate

Reaction of Zn(ClO4)2·6H2O with septadentate 2,6-bis[bis(2-benzimidazolylme-thyl)amino methyl]-4-methylphenol (Hbbap) and sodium isonicotinate yielded a dinuclear zinc complex[Zn2(bbap) (Iso) (Hiso)] (ClO4)2·[Zn2 (bbap) (Iso) (H2O)] (ClO4)2·4H2O(1a·1b·4H2O). Hiso isisonicotinic acid and Iso is isonicotinate anion. The structure has been established by X-raycrystallography and shows that the two zinc ions are bridged by the phenoxy unit of bbap- ligand,and the presence of unusual monodentate O-coordination of carboxylate group from isonicotinicacid. The coordination geometry around the zinc ion is approximately trigonal bipyramidal.

Chemical modifications of proteins and their applications in metalloenzyme studies

Protein chemical modifications are important tools for elucidating chemical and biological functions of proteins.Several strategies have been developed to implement these modifications,including enzymatic tailoring reactions,unnatural amino acid incorporation using the expanded genetic codes,and recognition-driven transformations.These technologies have been applied in metalloenzyme studies,specifically in dissecting their mechanisms,improving their enzymatic activities,and creating artificial enzymes with non-natural activities.Herein,we summarize some of the recent efforts in these areas with an emphasis on a few metalloenzyme case studies.

Ferriporphyrin-inspired MOFs as an artificial metalloenzyme for highly sensitive detection of H2O2 and glucose

Metalloenzymes which employ metal species and organic ligands as central active sites play significant roles in various biological activities.Development of artificial metalloenzymes can help to understand the related physiological mechanism and promote the applications of metalloenzymes in biosynthesis,energy conversion and biosensing.In this work,inspired by the active sites of ferriporphyrin-based metalloenzymes,Fe-MOFs by using ferric as the metal center and a porphyrin analog as the organic liga nd were developed as an artificial metalloenzyme.The Fe-MOFs exhibit high peroxidase-like catalytic activity with excellent long-term stability.Moreover,highly sensitive biosensors were built to detect H2 O2 and glucose based on the Fe-MOFs.Such MOFs-based artificial metalloenzyme offers an efficient strategy for the development of highly stable and efficient metalloenzymes,showing great potential in catalysis,energy transfer,biosensing and medical diagnosis.

AncPhore: A versatile tool for anchor pharmacophore steered drug discovery with applications in discovery of new inhibitors targeting metallo-β-lactamases and indoleamine/tryptophan 2,3-dioxygenases

We herein describe AncPhore,a versatile tool for drug discovery,which is characterized by pharmacophore feature analysis and anchor pharmacophore(i.e.,most important pharmacophore features)steered molecular fitting and virtual screening.Comparative analyses of numerous protein-ligand complexes using AncPhore revealed that anchor pharmacophore features are biologically important,commonly associated with protein conservative characteristics,and have significant contributions to the binding affinity.Performance evaluation of AncPhore showed that it had substantially improved prediction ability on different types of target proteins including metalloenzymes by considering the specific contributions and diversity of anchor pharmacophore features.To demonstrate the practicability of AncPhore,we screened commercially available chemical compounds and discovered a set of structurally diverse inhibitors for clinically relevant metallo-β-lactamases(MBLs);of them,4 and 6 manifested potent inhibitory activity to VIM-2,NDM-1 and IMP-1 MBLs.Crystallographic analyses of VIM-2:4 complex revealed the precise inhibition mode of 4 with VIM-2,highly consistent with the defined anchor pharmacophore features.Besides,we also identified new hit compounds by using AncPhore for indoleamine/tryptophan 2,3-dioxygenases(IDO/TDO),another class of clinically relevant metalloenzymes.This work reveals anchor pharmacophore as a valuable concept for target-centered drug discovery and illustrates the potential of AncPhore to efficiently identify new inhibitors for different types of protein targets.

A new method of NMR technique in the study of active center structure of metalloenzyme

UP until now, all methods using NMR technique to study the coordinated structure of activecenter in metalloenzyme are to reconstitute the diamagnetic ions [i. e. Zn(Ⅱ), etc.] in metal-loenzyme or its paramagnetic ions [i. e. Cu(Ⅱ), etc] whose electronic relaxation times are notshort enough to substitute the metal ions of active center in enzyme with [Co(Ⅱ), Ni(Ⅱ)],which are paramagnetic and whose electronic relaxation time is shorter, so that the ~1H NMRspectra of the coordinated structure of active center are separated from those of the rest of en-