Letters To The Editor
Cyclophilin B is really a major growth factor in breast milk
Cyclophilin B (CypB) was first described and its sequence was reported by Spik et al. in 1991 (1). These authors prepared and characterized recombinant CypB demonstrating that it had prolyl isomerase activity, which was inhibited by cyclosporin (1). At that time, no mitogenic activity was observed for CypB. This may be because of the absence of glycosylation, incorrect folding, denaturation, or to the cellular model used in these initial exploratory experiments (3T3). We wish to report that an earlier unpublished study (2) showed that CypB has growth factor activity on CCL-39 cells at around 30 ng/ml, similar to EGF, acidic FGF, and basic FGF.SARS-CoV-2 Y453F is not the “cluster 5” variant
I read with interest the recent publication by Bayarri-Olmos et al. (1) and would like to express some concerns regarding the study.Reply to Douglass and Spiegel: A suite of mathematical solutions to describe ternary complex formation and their application to targeted protein degredation by heterobifunctional ligands
Calculating equilibrium concentration of a ternary complex for a given total ligand concentration (1, 2) and predicting the ternary complex concentration in equilibrium with a given free ligand concentration (3) are two totally different questions that lead to clearly distinct mathematical solutions. Even though an exact solution to one question can be an approximate answer to the other, the latter approach (3) is consistent with a long-established tradition of analyzing equilibrium behavior of binding reactions: the equilibrium dissociation constants, Kds, that are used in both approaches are defined by the free, not total, ligand concentration at equilibrium, and the universally adopted equation for a bimolecular binding reaction, B = Bmax ∗ [L]/([L] + Kd), is also a function of free ligand concentration at equilibrium.Reply to Figueira et al.: Can NAD(P)+ transhydrogenase (NNT) mediate a physiologically meaningful increase in energy expenditure by mitochondria during H2O2 removal?
In our recent publication (1), as well as an earlier publication from our lab (2), we demonstrate under specific experimental conditions designed to increase flux through redox buffering circuits in mitochondria, and thus NADPH demand, that at least a portion of the accompanying increase in JO2 (i.e., proton conductance) is directly and reproducibly attributed to nicotinamide nucleotide transhydrogenase (NNT; e.g., Fig. 3D in (1)). In their letter to the editor, Figueira et al. question whether flux through redox circuits linked to NNT can mediate a meaningful increase in energy expenditure.Reply to Hayashi and Konishi: Noneffect of SARS-CoV-2 spike glycoprotein Y217N mutation on affinity between virus and ACE2
We thank Hayashi and Konishi for their comments and interest in our article (1). We agree that by structural modeling analysis, angiotensin-converting enzyme 2 (ACE2 [Y217N]) mutant shows no changes in binding with receptor-binding domain (RBD) when compared with WT ACE2, which is depicted in Figure 4 in our article. We think the lower binding affinity of human ACE2 N217 with RBD was due to the following reasons. First, cell surface abundance of ACE2 Y217N was less compared with WT ACE2 (Fig. 5 in our article).Noneffect of SARS-CoV-2 spike glycoprotein Y217N mutation on affinity between the virus and ACE2
The interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2), the primary entry receptor for SARS-CoV-2, is a key determinant of the range of hosts that can be infected by the virus. Zhang et al. (1) reportedly constructed human ACE2 (hACE2) with the Y217N mutation and found that this mutation completely blocked SARS-CoV-2 entry. Zhang et al. (1) performed an receptor binding domain (RBD) binding assay and found that WT hACE2 potently bound the RBD; however, hACE2 Y217N almost lost the ability to bind the RBD.Glycolysis and gluconeogenesis: A teaching view
I read with interest the recent review “Tracking the carbons supplying gluconeogenesis” by Ankit M. Shah and Fredric E. Wondisford (1). The figures are clear, and they are a good teaching source. Nevertheless, I note some potential teaching issues as well as offer additional suggestions. It is well known and it is explained to our students that there are three reactions of glycolysis that are essentially irreversible: hexokinase, phosphofrutokinase-1, and pyruvate kinase. Thus, I would like to observe in relation to Figure 1 thatReply to Hernández—Glycolysis and gluconeogenesis: A teaching view
We thank Félix Hernández for his insightful and thoughtful comments as well as interest in our manuscript (1). Regarding suggestion 1, we omitted several glycolytic and gluconeogenic enzymes in the figure for simplicity. We specifically mentioned G6Pase and PEPCK as many investigators have studied these enzymes in particular when studying gluconeogenesis. Articles specifically referenced in our review article studied these two enzymes, and we wished to pictorially represent these enzymes. We further described each of these two enzymes’ specific functions in the text.Statistical and thermodynamic analysis of the binding of trans-activation response–binding proteins to HIV-1 TAR RNA
In a recent article (1), the authors examine the binding of lab-evolved trans-activation response (TAR)–binding proteins (TBPs) to HIV-1 TAR RNA. Here, we show our analysis of the thermodynamic data of the binding that identifies three quantitative features of the binding, which may provide further insight into the interactions.where ΔH° and ΔS° are experimentally measured values reported in the original paper (1). Based on the statistical parameters, probability density of the ΔG° can be generated using Equation 2:where σ = 1.9407 kJ/mol and ΔG°mean = –41.3 kJ/mol.
