Modulation of fatty acid synthase by ATR checkpoint kinase Rad3

Steric occlusion regulates proximal interactions of acyl carrier protein domain in fungal fatty acid synthase

“…The structural domain of the ACP has so far only been observed to contact the structural insertion of the KS domain that forms part of the central α-disc of the FAS barrel 7,8 . The interaction of ACP with the ER 14,15 and AT 16 domains is shown to be mediated by its catalytic lobe, with no contacts between the structural lobe of the shuttling domain and the β-chains. The mode of interaction of ACP with ER is likely conserved between different species of fungi, as similar relative orientations have been observed in at least three different species (Fig.…”

“…Low resolution (~20 Å) densities with weak S/N are also observed in proximity of other catalytic centers in a cryoEM map of S. cerevisiae FAS 12 that allowed for approximate placement of ACP models in proximity of KS, ketoacyl reductase (KR), ER, and acetyltransferase (AT) domains albeit with ambiguity in ACP orientation. Recent cryoEM studies have observed sub-nanometer resolution ACP densities proximal to KS 13,14 , ER 14,15 , and AT 16 domains in the apo state of FAS enzymes purified from different fungal species.…”

Peripheral Linker Mediates Acyl Carrier Protein’s Recognition of Dehydratase and Stabilizes Type-I Mycobacterium tuberculosis Fatty Acid Synthase

“…These observations suggest that the structural core plays a role in stabilizing the interaction between ACP and DH, consistent with previous studies that suggested the important role played by the structural core in promoting the interaction between two domains when ACP is situated near KS or AT in FAS-I of SC and other fungal species. 29,32,52,53 We also observed one transient set of interactions established between ACP's residue on its fifth helix, ARG1844, and the DH residues from ASP1182 to ARG1187. This contact was established for 40% of the time in chain B of TMD2a, which undergoes event 1.…”

“…It is known to provide stability to the catalytic core and facilitate interaction via contributing to the surface area of the binding interface, while stalled at KS 29,32,52 and AT. 53 Lou et al were able to resolve the surface binding between the catalytic core of ACP and ER at a relatively higher resolution compared to that between the structural core of ACP and ER using cryo-EM on fungal FAS-I. 52 To unravel the molecular intricacies of the interactions between the structural core and DH, it is imperative to conduct a thorough investigation of the DH− ACP interaction.…”

Single-stranded RNA viruses activate and hijack host apical DNA damage response kinases for efficient viral replication

“…Recently, an antiviral drug screen identifies ATR kinase inhibitor as potent blocker of SARS-CoV-2 replication, which also inhibit replication of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV) as well (Garcia et al, 2021 ). Our long-term research focus on the ATM and ATR kinases (Qiu et al, 2019 ; Wang et al, 2016 ; Wang et al, 2017 ; Xin et al, 2019 ) prompted us to check whether ATM and/or ATR play a critical role in RNA virus replication. To unravel the putative molecular interplays between single-stranded RNA viruses’ replication and the host ATM and ATR kinases, we selected the in vitro replication model system of the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Zaire Ebolavirus (EBOV), which are the positive- and negative-sense single-stranded RNA viruses, respectively.…”