Single‐point mutation‐mediated local amphipathic adjustment dramatically enhances antibacterial activity of a fungal defensin

2016 ◽  
Vol 30 (7) ◽  
pp. 2602-2614 ◽  
Author(s):  
Jiajia Wu ◽  
Bin Gao ◽  
Shunyi Zhu
Keyword(s):  
Antibacterial Activity ◽  
Point Mutation ◽  
Single Point ◽  
Single Point Mutation ◽  
Fungal Defensin

scholarly journals A Fungal Defensin Targets the SARS−CoV−2 Spike Receptor−Binding Domain

2021 ◽  
Vol 7 (7) ◽  
pp. 553
Author(s):  
Bin Gao ◽  
Shunyi Zhu
Keyword(s):  
Receptor Binding ◽  
Viral Entry ◽  
Single Point ◽  
Binding Domain ◽  
Host Cells ◽  
Single Point Mutation ◽  
Binding Motif ◽  
Microsporum Canis ◽  
Receptor Binding Domain ◽  
Fungal Defensin

Coronavirus Disease 2019 (COVID−19) elicited by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS−CoV−2) is calling for novel targeted drugs. Since the viral entry into host cells depends on specific interactions between the receptor−binding domain (RBD) of the viral Spike protein and the membrane−bound monocarboxypeptidase angiotensin converting enzyme 2 (ACE2), the development of high affinity RBD binders to compete with human ACE2 represents a promising strategy for the design of therapeutics to prevent viral entry. Here, we report the discovery of such a binder and its improvement via a combination of computational and experimental approaches. The binder micasin, a known fungal defensin from the dermatophytic fungus Microsporum canis with antibacterial activity, can dock to the crevice formed by the receptor−binding motif (RBM) of RBD via an extensive shape complementarity interface (855.9 Å2 in area) with numerous hydrophobic and hydrogen−bonding interactions. Using microscale thermophoresis (MST) technique, we confirmed that micasin and its C−terminal γ−core derivative with multiple predicted interacting residues exhibited a low micromolar affinity to RBD. Expanding the interface area of micasin through a single point mutation to 970.5 Å2 accompanying an enhanced hydrogen bond network significantly improved its binding affinity by six−fold. Our work highlights the naturally occurring fungal defensins as an emerging resource that may be suitable for the development into antiviral agents for COVID−19.

scholarly journals A single point mutation converts a proton-pumping rhodopsin into a red-shifted, turn-on fluorescent sensor for chloride

2021 ◽  
Author(s):  
Jasmine N. Tutol ◽  
Jessica Lee ◽  
Hsichuan Chi ◽  
Farah N. Faizuddin ◽  
Sameera S. Abeyrathna ◽  
...  
Keyword(s):  
Point Mutation ◽  
Fluorescent Sensor ◽  
Single Point ◽  
Proton Pumping ◽  
Single Point Mutation ◽  
Turn On ◽  
Gloeobacter Violaceus

By utilizing laboratory-guided evolution, we have converted the fluorescent proton-pumping rhodopsin GR from Gloeobacter violaceus into GR1, a red-shifted, turn-on fluorescent sensor for chloride.

scholarly journals Structural basis for a complex I mutation that blocks pathological ROS production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhan Yin ◽  
Nils Burger ◽  
Duvaraka Kula-Alwar ◽  
Dunja Aksentijević ◽  
Hannah R. Bridges ◽  
...  
Keyword(s):  
Point Mutation ◽  
Complex I ◽  
Structural Changes ◽  
Ischemia Reperfusion ◽  
Single Point ◽  
Structural Basis ◽  
Single Point Mutation ◽  
Ros Production

AbstractMitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia–reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the “deactive” state, usually formed only after prolonged inactivity. Despite its tendency to adopt the “deactive” state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.

Scarcity of λ1 B cells in mice with a single point mutation in Cλ1 is due to a low BCR signal caused by misfolded lambda1 light chain

2007 ◽  
Vol 44 (6) ◽  
pp. 1417-1428 ◽  
Author(s):  
Veronica V. Volgina ◽  
Tianhe Sun ◽  
Grazyna Bozek ◽  
Terence E. Martin ◽  
Ursula Storb
Keyword(s):  
B Cells ◽  
Point Mutation ◽  
Light Chain ◽  
Single Point ◽  
Single Point Mutation

Shifting Substrate Specificity of Human Glutathione Transferase (from Class Pi to Class Alpha) by a Single Point Mutation

1998 ◽  
Vol 252 (1) ◽  
pp. 184-189 ◽  
Author(s):  
Marzia Nuccetelli ◽  
Anna P. Mazzetti ◽  
Jamie Rossjohn ◽  
Michael W. Parker ◽  
Philip Board ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Point Mutation ◽  
Glutathione Transferase ◽  
Single Point ◽  
Single Point Mutation
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