Results 51 to 60 of about 46,261 (289)

Mechanistic basis for inhibition of the extended‐spectrum β‐lactamase GES‐1 by enmetazobactam and tazobactam

FEBS Letters, EarlyView.
Antimicrobial resistance (AMR) is of huge importance, resulting in over 1 million deaths each year. Here, we describe how a new drug, enmetazobactam, designed to help fight resistant bacterial diseases, inhibits a key enzyme (GES‐1) responsible for AMR. Our data show it is a more potent inhibitor than the related tazobactam, with high‐level computation
Michael Beer, Philip Hinchliffe, Marko Hanževački, Christopher R. Bethel, Catherine L. Tooke, Marc W. Van der Kamp, Krisztina M. Papp‐Wallace, Robert A. Bonomo, Stuart Shapiro, Adrian J. Mulholland, James Spencer   +10 more
wiley   +1 more source

Gating mechanism of elongating β-ketoacyl-ACP synthases

Nature Communications, 2020
The formation of C-C bonds in fatty acid and polyketide biosynthesis depends on β-ketoacyl-acyl carrier protein (ACP) synthases (KSs). Here, the authors present structures of E.coli KSs bound to substrate mimetic bearing ACPs, providing insights into the
Jeffrey T. Mindrebo, Ashay Patel, Woojoo E. Kim, Tony D. Davis, Aochiu Chen, Thomas G. Bartholow, James J. La Clair, J. Andrew McCammon, Joseph P. Noel, Michael D. Burkart   +9 more
doaj   +1 more source

Subtractive genomics and molecular docking approach to identify drug targets against Stenotrophomonas maltophilia.

PLoS ONE, 2021
Stenotrophomonas maltophilia is a multidrug resistant pathogen associated with high mortality and morbidity in patients having compromised immunity. The efflux systems of S.
Hira Saleem, Usman Ali Ashfaq, Habibullah Nadeem, Muhammad Zubair, Muhammad Hussnain Siddique, Ijaz Rasul   +5 more
doaj   +1 more source

Mapping the evolution of mitochondrial complex I through structural variation

FEBS Letters, EarlyView.
Respiratory complex I (CI) is crucial for bioenergetic metabolism in many prokaryotes and eukaryotes. It is composed of a conserved set of core subunits and additional accessory subunits that vary depending on the organism. Here, we categorize CI subunits from available structures to map the evolution of CI across eukaryotes. Respiratory complex I (CI)
Dong‐Woo Shin, Tingting Chen, James A. Letts   +2 more
wiley   +1 more source

CoA‐dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases

EMBO Molecular Medicine, 2019
PKAN, CoPAN, MePAN, and PDH‐E2 deficiency share key phenotypic features but harbor defects in distinct metabolic processes. Selective damage to the globus pallidus occurs in these genetic neurodegenerative diseases, which arise from defects in CoA ...
Roald A Lambrechts, Hein Schepers, Yi Yu, Marianne van der Zwaag, Kaija J Autio, Marcel A Vieira‐Lara, Barbara M Bakker, Marina A Tijssen, Susan J Hayflick, Nicola A Grzeschik, Ody CM Sibon   +10 more
doaj   +1 more source

Linked dimers of the AAA+ ATPase Msp1 reveal energetic demands and mechanistic plasticity for substrate extraction from lipid bilayers

FEBS Letters, EarlyView.
Cells must clear mislocalized or faulty proteins from membranes to survive. The AAA+ ATPase Msp1 performs this task, but dissecting how its six subunits work together is challenging. We engineered linked dimers with varied numbers of functional subunits to reveal how Msp1 subunits cooperate and use energy to extract proteins from the lipid bilayer ...
Deepika Gaur, Brian Acquaviva, Baylee A. Smith, Nathan Walker, Isabella Walter, Matthew L. Wohlever   +5 more
wiley   +1 more source

Remote control of regioselectivity in acyl-acyl carrier protein-desaturases [PDF]

Proceedings of the National Academy of Sciences, 2011
Regiospecific desaturation of long-chain saturated fatty acids has been described as approaching the limits of the discriminatory power of enzymes because the substrate entirely lacks distinguishing features close to the site of dehydrogenation.
Ylva Lindqvist, Johan Lengqvist, John Shanklin, Martin Moche, Jodie E. Guy, Edward Whittle   +5 more
openaire   +2 more sources

Reciprocal control of viral infection and phosphoinositide dynamics

FEBS Letters, EarlyView.
Phosphoinositides, although scarce, regulate key cellular processes, including membrane dynamics and signaling. Viruses exploit these lipids to support their entry, replication, assembly, and egress. The central role of phosphoinositides in infection highlights phosphoinositide metabolism as a promising antiviral target.
Marie Déborah Bancilhon, Bruno Mesmin
wiley   +1 more source

Phosphomimetic mutations near active sites of proteins in Thermus thermophilus suggest a widespread regulatory mechanism

FEBS Open Bio, EarlyView.
In Thermus thermophilus, more than half of the phosphorylation sites identified by proteomic analysis are located near the active site. All phosphomimetic mutants of phosphosites of six enzymes belonging to different families showed severely reduced activity compared with the wild‐type, particularly in the turnover number.
Anzu Nishiwaki, Hiroki Okanishi, Yoshikatsu Kanai, Ryoji Masui   +3 more
wiley   +1 more source

Short‐term actions of epigalocatechin‐3‐gallate in the liver: a mechanistic insight into hypoglycemic and potential toxic effects

FEBS Open Bio, EarlyView.
Epigallocatechin‐3‐gallate (EGCG) acutely inhibited gluconeogenesis and enhanced glycolysis, glycogenolysis, and fatty acid oxidation in perfused rat livers. Mechanistic assays revealed mitochondrial uncoupling, inhibition of pyruvate carboxylation and glucose‐6‐phosphatase, shift of NADH/NAD+ ratios toward oxidation, and loss of membrane integrity ...
Carla Indianara Bonetti, Bruna Lopes Correia, Francielle Cristina Nakamura Manicardi, Nairana Mithieli de Queiroz Eskuarek Melo, Vanesa de Oliveira Pateis, Jurandir Fernando Comar, Anacharis Babeto de Sá‐Nakanishi, Adelar Bracht, Lívia Bracht   +8 more
wiley   +1 more source