EPR Study of Substrate Binding to the Mn(II) Active Site of the Bacterial Antibiotic Resistance Enzyme FosA:  A Better Way To Examine Mn(II)

2002 ◽  
Vol 124 (10) ◽  
pp. 2318-2326 ◽  
Author(s):  
Stoyan K. Smoukov ◽  
Joshua Telser ◽  
Bryan A. Bernat ◽  
Chris L. Rife ◽  
Richard N. Armstrong ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Active Site ◽  
Substrate Binding ◽  
Bacterial Antibiotic Resistance

scholarly journals A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding

2020 ◽  
Vol 6 (26) ◽  
pp. eaaz9861 ◽  
Author(s):  
Stanislav S. Terekhov ◽  
Yuliana A. Mokrushina ◽  
Anton S. Nazarov ◽  
Alexander Zlobin ◽  
Arthur Zalevsky ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Microbial Communities ◽  
Active Site ◽  
Substrate Binding ◽  
Catalytic Efficiency ◽  
Crystallographic Analysis ◽  
Diffusion Limit ◽  
Substrate Affinity ◽  
Multiscale Simulations ◽  
Substrate Promiscuity

Microbial communities are self-controlled by repertoires of lethal agents, the antibiotics. In their turn, these antibiotics are regulated by bioscavengers that are selected in the course of evolution. Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. A new subfamily of AmiN-like kinases, isolated from the Siberian bear microbiome, inactivates antibiotic amicoumacin by phosphorylation. The nanomolar substrate affinity defines AmiN as a phosphotransferase with a unique catalytic efficiency proximal to the diffusion limit. Crystallographic analysis and multiscale simulations revealed a catalytically perfect mechanism providing phosphorylation exclusively in the case of a closed active site that counteracts substrate promiscuity. AmiN kinase is a member of the previously unknown subfamily representing the first evidence of a specialized phosphotransferase bioscavenger.

scholarly journals Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

2021 ◽  
Vol 14 (5) ◽  
pp. 420
Author(s):  
Tanveer Ali ◽  
Abdul Basit ◽  
Asad Mustafa Karim ◽  
Jung-Hun Lee ◽  
Jeong-Ho Jeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Active Site ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Meca Gene ◽  
Resistance Mechanism ◽  
Ligand Docking ◽  
Clinical Samples ◽  
Allosteric Site ◽  
Methicillin Resistant

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.

scholarly journals Predicting allosteric mutants that increase activity of a major antibiotic resistance enzyme

2017 ◽  
Vol 8 (9) ◽  
pp. 6484-6492 ◽  
Author(s):  
M. J. Latallo ◽  
G. A. Cortina ◽  
S. Faham ◽  
R. K. Nakamoto ◽  
P. M. Kasson
Keyword(s):  
Machine Learning ◽  
Antibiotic Resistance ◽  
Active Site ◽  
Beta Lactamase ◽  
Active Site Residues ◽  
Conformational Ensembles

Allosteric mutations increasingkcatin a beta lactamase act by changing conformational ensembles of active-site residues identified by machine learning.

Substrate-binding specificity of chitinase and chitosanase as revealed by active-site architecture analysis

2015 ◽  
Vol 418 ◽  
pp. 50-56 ◽  
Author(s):  
Shijia Liu ◽  
Shangjin Shao ◽  
Linlin Li ◽  
Zhi Cheng ◽  
Li Tian ◽  
...  
Keyword(s):  
Active Site ◽  
Substrate Binding ◽  
Binding Specificity ◽  
Architecture Analysis
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