Ask about this productRelated genes to: SDSL Blocking Peptide
- Gene:
- SDSL NIH gene
- Name:
- serine dehydratase like
- Previous symbol:
- -
- Synonyms:
- SDS-RS1, cSDH
- Chromosome:
- 12q24.13
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-16
- Date modifiied:
- 2016-03-11
Related products to: SDSL Blocking Peptide
Related articles to: SDSL Blocking Peptide
- Intrinsically disordered proteins (IDPs) often use charge-patterned polyampholyte regions to couple concentration and ionic strength to conformational changes, but the mechanisms by which such regions redistribute secondary-structure elements and modulate local dynamics remain incompletely understood. Here, we use the yeast vacuolar aspartyl protease inhibitor IA3 as a minimal model to dissect how a C-terminal polyampholyte controls the conformational ensemble and dynamics of a helix-forming N-terminal inhibitory segment. IA3 comprises a conserved N-terminal binding helix (residues 1-32), a mixed-charge linker (residues 33-49), and a near-neutral C-terminal polyampholyte (residues 50-68). We show by far-UV circular dichroism (CD) spectroscopy and BeStSel deconvolution that, at very low ionic strength, increasing IA3 concentration from 10 to 100 μM drives a reversible redistribution from helix/turn-enriched to antiparallel/coil-enriched ensembles, without visible phase separation. Raising salt to moderate levels recapitulates these high-concentration spectra at low micromolar IA3, indicating that electrostatic screening effectively reduces the interaction-driven "effective concentration" of chains. Single-site charge substitutions in the C-terminal region (D46K, E68N) reproduce the high-concentration ensemble at 10 μM, whereas other mutations (N52E, K61D, L60K, K24L) preserve the low-concentration, helix/turn-rich state. Site-directed spin-labeling electron paramagnetic resonance (SDSL-EPR) at position 9 within the inhibitory helix reveals that conditions favoring antiparallel/other-rich ensembles increase local mobility, whereas helix/turn-enriched states exhibit more restricted motion. These results establish IA3 as a minimal system in which a C-terminal polyampholyte functions as a tunable electrostatic sensor, coupling charge patterning, concentration, and ionic strength to secondary-structure redistribution and N-terminal helix dynamics. The findings define sequence-encoded electrostatic rules that may generalize to other polyampholyte-containing IDPs and suggest how IA3 couples its inhibitory activity to cellular ionic conditions. - Source: PubMed
Jaufer AfnanSilva Larissa OLi TianyanKumarasinghe IshaniDunleavy Katie MFanucci Gail E - Mechanosensitive (MS) channels are membrane proteins that respond to mechanical stimuli and are essential across prokaryotic and eukaryotic organisms. The mechanosensitive channel of large conductance (MscL) provides a powerful model for dissecting protein-lipid interactions underlying mechanotransduction. Here, we investigated the contribution of four periplasmic loop residues (A64, Q65, G66, D67) to MscL gating. Using site-directed spin labelling (SDSL) and electron paramagnetic resonance (EPR) spectroscopy, we show that these residues interact directly with the lipid bilayer during the channel opening through membrane tension sensitivity of the channel. We further examined how mutations at these periplasmic loop residues affect biophysical properties of MscL in giant spheroplasts and liposomes composed of azolectin or negatively charged lipids (70% phosphatidylcholine and 30% phosphatidylglycerol) using patch clamp electrophysiology, patch fluorometry and molecular dynamics simulations. Substitution of Q65 residue with arginine (Q65R) increased channel sensitivity to membrane tension, whereas replacement with glutamic acid (Q65E) decreased the sensitivity across all systems tested. Molecular dynamics simulations revealed that under in-plane radial tension Q65E exhibited larger conformational changes under tension, whereas the wild-type (WT) and Q65R mutant channels showed rapid and extensive opening at later stages within a shorter time frame. Insertion of a four-glycine hinge at D67 also reduced tension sensitivity, consistent with impaired force transmission. Substitution of A64 and G66 to either glutamic acid (A64E, G66E) or arginine (A64R) decreased tension sensitivity of the channel only in liposomes of negatively charged lipids. Together, these findings deepen our understanding of protein-lipid interactions governing MscL opening kinetics and highlights the contribution of the periplasmic loop in regulating mechanosensitivity. - Source: PubMed
Publication date: 2026/05/05
Duru Kingsley CRohde Paul RHafezi HoomanBavi OmidBavi NavidMartinac Boris - The structural flexibility of enzymes plays an essential role in determining their catalytic efficiency and thermal stability. Cold-adapted enzymes are typically highly flexible, resulting in high catalytic activity but low stability. Glucokinase (GK) consists of the large substrates binding domain, small catalytic domain, and hinge region that undergoes conformational changes upon substrates binding. We recently reported that the psychrophilic GK from sp. AS-131 (PsGK) exhibits both high catalytic efficiency and remarkable thermal stability compared to the mesophilic GK from (EcGK). We also found that a disulfide bond connecting the N- and C-termini in PsGK contributes to its unusual thermal stability. However, cold adaptation mechanism of cold-adapted PsGK has remained unclear. To clarify how PsGK acquires high activity, we utilized site-directed spin labeling electron spin resonance (SDSL-ESR) spectroscopy for PsGK and EcGK in the absence and presence of substrates in the wide range of temperatures. PsGK without substrates was more flexible than EcGK. Particularly, the small domain and hinge region of PsGK were highly flexible while its large domain was relatively rigid. In contrast, EcGK showed lower entire flexibility and did not exhibit domain dependent differences. When the substrates were bound, both enzymes became more rigid, but the small domain and hinge region of PsGK was still flexible whereas its large domain was considerably rigid. These results suggest that enhancing catalytic activity requires increasing flexibility only in proper sites rather than in the entire enzyme. These findings provide insight into how cold-adapted enzymes balance activity and stability. - Source: PubMed
Publication date: 2026/02/17
Yato AkaneHoritani Masaki - In vertebrate phototransduction, the G protein-coupled receptor rhodopsin activates the α-subunit of transducin (Gα ), which, upon binding the γ-subunits of phosphodiesterase-6 (PDE6), stimulates cGMP hydrolysis. We reported a cryoEM structure for a complex containing two constitutively active Gα (Gα *) subunits coupled by a bivalent antibody bound to PDE6 that demonstrated a striking displacement of both PDEγ subunits from the PDEα/PDEβ catalytic sites and suggested an alternating-site mechanism for PDE6 activation. Here, we use site-directed spin labeling (SDSL) and double electron-electron resonance spectroscopy (DEER) to probe PDE6 conformational changes upon Gα * binding. PDEγ spin-labelled on Cys68 and Ile64Cys demonstrate that PDEγ have highly flexible C-termini that transiently bind to the PDEα/PDEβ heterodimer. Binding of Gα * to PDE6 with the inhibitor udenafil occupying its catalytic sites alters the positions of the PDEγ subunits in agreement with the changes shown in the cryoEM structure for this complex, whereas coupling the Gα * subunits to the bivalent antibody does not affect the DEER distributions observed for PDE6 bound to Gα *. However, binding of the slow hydrolyzing 8-Br-cGMP substrate in the presence of Gα * causes a dramatic increase in the separation and spread of the spin-labelled PDEγ subunits, thereby revealing a previously unobserved conformation of PDE6 associated with catalysis, which is further supported by small angle X-ray scattering (SAXS) analysis. These studies indicate that whereas inhibitors trap Gα *-PDE6 complexes in an inactive state as represented by the cryoEM structure, the binding of both substrate and Gα * produces a dynamic active state consistent with an alternating-site mechanism. - Source: PubMed
Publication date: 2026/05/04
Holechek Jessica NShang Julia YAssafa Tufa ECrane Brian RCerione Richard A - Calcium oxalate calculi constitute the predominant form of kidney stones, yet the molecular pathways governing their formation are not fully understood. Growing evidence suggests that these crystalline deposits can trigger apoptotic pathways in renal tubular epithelial cells. Within this pathological context, various amino acid metabolic pathways significantly influence cellular viability. This study seeks to elucidate the involvement of serine metabolism in endoplasmic reticulum stress (ERS), reactive oxygen species (ROS) production, and the ensuing apoptosis in renal tubular epithelial cells, along with delineating its mechanistic basis. - Source: PubMed
Publication date: 2026/04/01
Yan XuLi GuoxiangWang ZhenLi CunyaoShi YongYan XinyuLi RongWen BoJing JunfengQi WeiYi XinchengXi JunhuaZhang Yanbin