scholarly journals The AAA ATPase Vps4 binds ESCRT-III substrates through a repeating array of dipeptide-binding pockets

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Han Han ◽  
Nicole Monroe ◽  
Wesley I Sundquist ◽  
Peter S Shen ◽  
Christopher P Hill
Keyword(s):  
Hydrogen Bonds ◽  
Main Chain ◽  
Substrate Binding ◽  
Conveyor Belt ◽  
Side Chain ◽  
Peptide Substrate ◽  
Aaa Atpase ◽  
Membrane Fission ◽  
Wide Range ◽  
Binding Pockets

The hexameric AAA ATPase Vps4 drives membrane fission by remodeling and disassembling ESCRT-III filaments. Building upon our earlier 4.3 Å resolution cryo-EM structure (<xref ref-type="bibr" rid="bib29">Monroe et al., 2017</xref>), we now report a 3.2 Å structure of Vps4 bound to an ESCRT-III peptide substrate. The new structure reveals that the peptide approximates a β-strand conformation whose helical symmetry matches that of the five Vps4 subunits it contacts directly. Adjacent Vps4 subunits make equivalent interactions with successive substrate dipeptides through two distinct classes of side chain binding pockets formed primarily by Vps4 pore loop 1. These pockets accommodate a wide range of residues, while main chain hydrogen bonds may help dictate substrate-binding orientation. The structure supports a ‘conveyor belt’ model of translocation in which ATP binding allows a Vps4 subunit to join the growing end of the helix and engage the substrate, while hydrolysis and release promotes helix disassembly and substrate release at the lagging end.

scholarly journals Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Albert Escobedo ◽  
Busra Topal ◽  
Micha B. A. Kunze ◽  
Juan Aranda ◽  
Giulio Chiesa ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hydrogen Bonds ◽  
Main Chain ◽  
Side Chain

Destabilization of the 310-Helix in Peptides Based on Cα-Tetrasubstituted α-Amino Acids by Main-Chain to Side-Chain Hydrogen Bonds

1998 ◽  
Vol 120 (45) ◽  
pp. 11558-11566 ◽  
Author(s):  
Wojciech M. Wolf ◽  
Marcin Stasiak ◽  
Miroslav T. Leplawy ◽  
Alberto Bianco ◽  
Fernando Formaggio ◽  
...  
Keyword(s):  
Amino Acids ◽  
Hydrogen Bonds ◽  
Main Chain ◽  
Side Chain ◽  
310 Helix

scholarly journals Glutamine Side-Chain to Main Chain Hydrogen Bonds Can be used to Design Single Alpha-Helices that are Stable at Room Temperature

2020 ◽  
Vol 118 (3) ◽  
pp. 369a-370a
Author(s):  
Albert Escobedo ◽  
Busra Topal ◽  
Micha Kunze ◽  
Juan Aranda ◽  
Giulio Chiesa ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Room Temperature ◽  
Main Chain ◽  
Side Chain ◽  
Alpha Helices

scholarly journals Carbohydrate Kinases: A Conserved Mechanism Across Differing Folds

Catalysts ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Sumita Roy ◽  
Mirella Vivoli Vega ◽  
Nicholas J. Harmer
Keyword(s):  
Hydrogen Bonds ◽  
Divalent Cation ◽  
Side Chain ◽  
Control Points ◽  
Critical Control Points ◽  
Wide Range ◽  
Common Strategy ◽  
Network Of Hydrogen Bonds ◽  
Main Protein ◽  
Positively Charged

Carbohydrate kinases activate a wide variety of monosaccharides by adding a phosphate group, usually from ATP. This modification is fundamental to saccharide utilization, and it is likely a very ancient reaction. Modern organisms contain carbohydrate kinases from at least five main protein families. These range from the highly specialized inositol kinases, to the ribokinases and galactokinases, which belong to families that phosphorylate a wide range of substrates. The carbohydrate kinases utilize a common strategy to drive the reaction between the sugar hydroxyl and the donor phosphate. Each sugar is held in position by a network of hydrogen bonds to the non-reactive hydroxyls (and other functional groups). The reactive hydroxyl is deprotonated, usually by an aspartic acid side chain acting as a catalytic base. The deprotonated hydroxyl then attacks the donor phosphate. The resulting pentacoordinate transition state is stabilized by an adjacent divalent cation, and sometimes by a positively charged protein side chain or the presence of an anion hole. Many carbohydrate kinases are allosterically regulated using a wide variety of strategies, due to their roles at critical control points in carbohydrate metabolism. The evolution of a similar mechanism in several folds highlights the elegance and simplicity of the catalytic scheme.

scholarly journals Hydrogen Bonding in a l-Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 881
Author(s):  
Federica Lazzari ◽  
Amedea Manfredi ◽  
Jenny Alongi ◽  
Fabio Ganazzoli ◽  
Francesca Vasile ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Main Chain ◽  
Variable Temperature ◽  
Dipole Moments ◽  
Md Simulations ◽  
Side Chain ◽  
2D Noesy ◽  
Diffusion Studies ◽  
Ph Dependent ◽  
Nmr Diffusion

This paper reports on synthesis, acid–base properties, and self-structuring in water of a chiral polyamidoamino acid, M-l-Gln, obtained from the polyaddition of N,N′-methylenebisacrylamide with l-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-l-Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents. The NMR diffusion studies were consistent with a population of unimolecular nanoparticles thus excluding aggregation. The M-l-Gln had the highest molecular weight and hydrodynamic radius among all polyamidoamino acids described. Possibly, transient hydrogen bonds between l-glutamine molecules and M-l-Gln growing chains facilitated the polyaddition reaction. Theoretical modeling showed that M-l-Gln assumed pH-dependent self-ordered coil conformations with main chain transoid arrangements reminiscent of the protein hairpin motif owing to intramolecular dipole moments and hydrogen bonds. The latter were most numerous at the isoelectric point (pH 4.5), where they mainly involved even topologically distant main chain amide N–H and side chain amide C=O brought to proximity by structuring. Hydrogen bonds at pH 4.5 were also suggested by variable temperature NMR. The 2D NOESY experiments at pH 4.5 confirmed the formation of compact structures through the analysis of the main chain/side chain hydrogen contacts, in line with MD simulations.

scholarly journals Substrate Scope for Human Histone Lysine Acetyltransferase KAT8

2021 ◽  
Vol 22 (2) ◽  
pp. 846
Author(s):  
Giordano Proietti ◽  
Yali Wang ◽  
Chiara Punzo ◽  
Jasmin Mecinović
Keyword(s):  
Main Chain ◽  
Coenzyme A ◽  
Side Chain ◽  
Histone H4 ◽  
Chemical Probes ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Histone Lysine ◽  
Lysine Acetyltransferase

Biomedically important histone lysine acetyltransferase KAT8 catalyses the acetyl coenzyme A-dependent acetylation of lysine on histone and other proteins. Here, we explore the ability of human KAT8 to catalyse the acetylation of histone H4 peptides possessing lysine and its analogues at position 16 (H4K16). Our synthetic and enzymatic studies on chemically and structurally diverse lysine mimics demonstrate that KAT8 also has a capacity to acetylate selected lysine analogues that possess subtle changes on the side chain and main chain. Overall, this work highlights that KAT8 has a broader substrate scope beyond natural lysine, and contributes to the design of new chemical probes targeting KAT8 and other members of the histone lysine acetyltransferase (KAT) family.

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