Author Correction: Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action

AbstractHuman Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of l-arginine to l-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.

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Insight into the Mechanism of Action of Heparin Cofactor II

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649913 ◽

1995 ◽

Vol 74 (05) ◽

pp. 1209-1214 ◽

Cited By ~ 74

Author(s):

Douglas M Tollefsen

Keyword(s):

Mechanism Of Action ◽

Heparin Cofactor Ii ◽

Insight Into

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A Molecular Insight into the Synergistic Mechanism of Nigella sativa (Black Cumin) with β-Lactam Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

Applied Sciences ◽

10.3390/app11073206 ◽

2021 ◽

Vol 11 (7) ◽

pp. 3206

Author(s):

Lorina I. Badger-Emeka ◽

Promise Madu Emeka ◽

Hairul Islam M. Ibrahim

Keyword(s):

Staphylococcus Aureus ◽

Mechanism Of Action ◽

Methicillin Resistant Staphylococcus Aureus ◽

Nigella Sativa ◽

Synergistic Effects ◽

Diffusion Method ◽

Methicillin Resistant ◽

Cell Wall Disruption ◽

Time Kill ◽

Insight Into

Methicillin-resistant Staphylococcus aureus (MRSA) infection is detrimental to hospitalized patients. With diminishing choices of antibiotics and the worry about resistance to colistin in synergistic combined therapy, there are suggestions for the use of herbal derivatives. This investigation evaluated the synergistic effects of Nigella sativa (NS) in combination with beta-lactam (β-lactam) antibiotics on extreme drug-resistant (XDR) MRSA isolates. NS concentrations of 10, 7.5, 5.0, 2.5, 1.0, and 0.1 µg/mL, alone and in combination with β-lactam antibiotics, were used to determine the antimicrobial susceptibility of MRSA isolates by the well diffusion method. Time–kill assays were performed using a spectrophotometer, with time–kill curves plotted and synergism ascertained by the fractional inhibitory concentration (FIC). Scanning and transmission electron microscopy were used to gain insight into the mechanism of action of treated groups. Isolates were inhibited by the NS concentrations, with differences in the zones of inhibition being statistically insignificant at p < 0.05. There were statistically significant differences in the time–kill assay for the MRSA isolates. In addition, NS combined with augmentin showed better killing than oxacillin and cefuroxime. The mechanism of action shown by the SEM and TEM results revealed cell wall disruption, which probably created interference that led to bacterial lysis.

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Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers ◽

10.3390/cancers13143540 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3540

Author(s):

Hamid Maadi ◽

Mohammad Hasan Soheilifar ◽

Won-Shik Choi ◽

Abdolvahab Moshtaghian ◽

Zhixiang Wang

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Cancer Patients ◽

Mechanism Of Action ◽

Mechanisms Of Action ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Insight Into ◽

Positive Breast Cancer

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

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