Folding control of a non-natural glycopeptide using saccharide-coded structural information for polypeptides

2020 ◽  
Vol 56 (18) ◽  
pp. 2767-2770 ◽  
Author(s):  
Yuki Ishido ◽  
Naoya Kanbayashi ◽  
Naoka Fujii ◽  
Taka-aki Okamura ◽  
Takeharu Haino ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Main Chain ◽  
Structural Information ◽  
Side Chain ◽  
Folding Structure

We synthesized “glyco-arylopeptides”, whose folding structure significantly changes depending on the kind of saccharide in their side chain. The saccharide moiety interacts with the main chain via hydrogen bonding, and the non-natural polypeptides form two well-defined architectures—(P)-31- and (M)-41-helices—depending on the length of the saccharide chains and even the configuration of a single stereo-genic center in the epimers.

scholarly journals Side-Chain to Main-Chain Hydrogen Bonding Controls the Intrinsic Backbone Dynamics of the Amyloid Precursor Protein Transmembrane Helix

2014 ◽  
Vol 106 (6) ◽  
pp. 1318-1326 ◽  
Author(s):  
Christina Scharnagl ◽  
Oxana Pester ◽  
Philipp Hornburg ◽  
Daniel Hornburg ◽  
Alexander Götz ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Amyloid Precursor Protein ◽  
Main Chain ◽  
Transmembrane Helix ◽  
Precursor Protein ◽  
Backbone Dynamics ◽  
Side Chain

scholarly journals Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ho Yee Joyce Fung ◽  
Szu-Chin Fu ◽  
Yuh Min Chook
Keyword(s):  
Hydrogen Bonding ◽  
Crystal Structures ◽  
Nuclear Export ◽  
Main Chain ◽  
Side Chain ◽  
Large Array ◽  
Structural Element ◽  
Binding Groove ◽  
Nuclear Export Receptor ◽  
Hydrophobic Anchor

Nuclear export receptor CRM1 binds highly variable nuclear export signals (NESs) in hundreds of different cargoes. Previously we have shown that CRM1 binds NESs in both polypeptide orientations (Fung et al., 2015). Here, we show crystal structures of CRM1 bound to eight additional NESs which reveal diverse conformations that range from loop-like to all-helix, which occupy different extents of the invariant NES-binding groove. Analysis of all NES structures show 5-6 distinct backbone conformations where the only conserved secondary structural element is one turn of helix that binds the central portion of the CRM1 groove. All NESs also participate in main chain hydrogen bonding with human CRM1 Lys568 side chain, which acts as a specificity filter that prevents binding of non-NES peptides. The large conformational range of NES backbones explains the lack of a fixed pattern for its 3-5 hydrophobic anchor residues, which in turn explains the large array of peptide sequences that can function as NESs.

scholarly journals Charged histidine affects alpha-helix stability at all positions in the helix by interacting with the backbone charges

1993 ◽  
Vol 90 (23) ◽  
pp. 11337-11340 ◽  
Author(s):  
K M Armstrong ◽  
R L Baldwin
Keyword(s):  
Hydrogen Bonding ◽  
Central Region ◽  
Main Chain ◽  
Alpha Helix ◽  
Dipole Interaction ◽  
Major Effect ◽  
Side Chain ◽  
Histidine Residue ◽  
Helix Stability

To determine whether a charged histidine side chain affects alpha-helix stability only when histidine is close to one end of the helix or also when it is in the central region, we substitute a single histidine residue at many positions in two reference peptides and measure helix stability and histidine pKa. The position of a charged histidine residue has a major effect on helix stability in 0.01 M NaCl: the helix content of a 17-residue peptide is 24% when histidine is at position 3 compared to 76% when it is at position 17. This dependence of helix content on histidine position decreases sharply in 1 M NaCl, as expected for counterion screening of the charge-helix dipole interaction. Results at interior positions indicate that the position of a charged histidine residue affects helix stability at these positions. Unexpectedly high values of the helix content are found when either neutral or charged histidine is at one of the last three C-terminal positions, suggesting that either form can stabilize an isolated helix by hydrogen bonding to a main-chain CO group.

Influence of hydrogen bonding, main chain-side chain interactions, and protecting groups on the excimer formation of bis(pyrenylalanine) peptides

Biopolymers ◽  
1987 ◽  
Vol 26 (11) ◽  
pp. 1833-1857 ◽  
Author(s):  
R. Goedeweeck ◽  
F. Ruttens ◽  
F. López-Arbeloa ◽  
F. C. De Schryver
Keyword(s):  
Hydrogen Bonding ◽  
Main Chain ◽  
Protecting Groups ◽  
Side Chain ◽  
Excimer Formation

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.

The significance of the Cα substituent in the selective inhibition of matrix metalloproteinases 1 and 9

2011 ◽  
Vol 392 (11) ◽  
Author(s):  
Riyad Domingo ◽  
Kelly Chibale ◽  
Edward D. Sturrock
Keyword(s):  
Hydrogen Bonding ◽  
Matrix Metalloproteinases ◽  
Active Sites ◽  
Unsaturated Compound ◽  
Selective Inhibition ◽  
Acid Group ◽  
Side Chain ◽  
Carboxylic Acid Group ◽  
Lead Compounds ◽  
Hydrogen Bonding Interactions

Abstract Matrix metalloproteinases (MMPs) cleave and degrade most components of the extracellular matrix, and unregulated MMP activity has been correlated to cancer and metastasis. Hence there is a burgeoning need to develop inhibitors that bind selectively to structurally similar MMPs. The inhibition profiles of peptidomimetics containing Cα substituents at the α,β unsaturated carbon were evaluated against the recombinant forms of ADAM17, MMP1, and MMP9. The dicarboxylic acid D2 and hydroxamate C2 inhibited MMP9 but not MMP1. The unsaturated compound E2 displayed selective inhibition for MMP1, compared with the saturated precursor C2, with an IC50 value of 3.91 μm. The molecular basis for this selectivity was further investigated by the molecular docking of E2 and D2 into the active sites of MMP1 and MMP9. These data demonstrate hydrogen-bonding interactions between the carbonyl group of the Cα substituent of E2 and the side chain of Asn180 present in the active site of MMP1. Conversely, the docked MMP9-D2 structure shows hydrophobic and hydrogen bonding between the ligand’s morpholine substituent and second carboxylic acid group with Leu187 and an amide, respectively. This study suggests that substituents other than P1′ and P2′ may confer selectivity among MMPs and may aid in the search for novel lead compounds.

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