Cystinophanes, a Novel Family of Aromatic-Bridged Cystine Cyclic Peptides:  Synthesis, Crystal Structure, Molecular Recognition, and Conformational Studies

1998 ◽  
Vol 120 (12) ◽  
pp. 2695-2702 ◽  
Author(s):  
Darshan Ranganathan ◽  
V. Haridas ◽  
Isabella L. Karle
Keyword(s):  
Crystal Structure ◽  
Molecular Recognition ◽  
Cyclic Peptides ◽  
Conformational Studies ◽  
Peptides Synthesis

scholarly journals Structural and functional studies of Arabidopsis thaliana legumain beta reveal isoform specific mechanisms of activation and substrate recognition

2020 ◽  
Vol 295 (37) ◽  
pp. 13047-13064 ◽  
Author(s):  
Elfriede Dall ◽  
Florian B. Zauner ◽  
Wai Tuck Soh ◽  
Fatih Demir ◽  
Sven O. Dahms ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Arabidopsis Thaliana ◽  
Cyclic Peptides ◽  
Molecular Mechanisms ◽  
Functional Studies ◽  
Plant Characteristic ◽  
Activation Mechanisms ◽  
Binding Pockets ◽  
First Time ◽  
Autocatalytic Activation

The vacuolar cysteine protease legumain plays important functions in seed maturation and plant programmed cell death. Because of their dual protease and ligase activity, plant legumains have become of particular biotechnological interest, e.g. for the synthesis of cyclic peptides for drug design or for protein engineering. However, the molecular mechanisms behind their dual protease and ligase activities are still poorly understood, limiting their applications. Here, we present the crystal structure of Arabidopsis thaliana legumain isoform β (AtLEGβ) in its zymogen state. Combining structural and biochemical experiments, we show for the first time that plant legumains encode distinct, isoform-specific activation mechanisms. Whereas the autocatalytic activation of isoform γ (AtLEGγ) is controlled by the latency-conferring dimer state, the activation of the monomeric AtLEGβ is concentration independent. Additionally, in AtLEGβ the plant-characteristic two-chain intermediate state is stabilized by hydrophobic rather than ionic interactions, as in AtLEGγ, resulting in significantly different pH stability profiles. The crystal structure of AtLEGβ revealed unrestricted nonprime substrate binding pockets, consistent with the broad substrate specificity, as determined by degradomic assays. Further to its protease activity, we show that AtLEGβ exhibits a true peptide ligase activity. Whereas cleavage-dependent transpeptidase activity has been reported for other plant legumains, AtLEGβ is the first example of a plant legumain capable of linking free termini. The discovery of these isoform-specific differences will allow us to identify and rationally design efficient ligases with application in biotechnology and drug development.

Propargyloxyproline Regio- and Stereoisomers for Click-Conjugation of Peptides: Synthesis and Application in Linear and Cyclic Peptides

2015 ◽  
Vol 68 (9) ◽  
pp. 1365 ◽  
Author(s):  
Susan E. Northfield ◽  
Simon J. Mountford ◽  
Jerome Wielens ◽  
Mengjie Liu ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Peptide Synthesis ◽  
Cyclic Peptides ◽  
Click Reaction ◽  
Fluorescent Labels ◽  
Peptide Conjugates ◽  
Conformational Properties ◽  
Peptides Synthesis

The use of the click reaction for the introduction of conjugate groups, such as affinity or fluorescent labels, to a peptide for the study of peptide biochemistry and pharmacology is widespread. However, the nature and location of substituted 1,2,3-triazoles in peptide sequences may markedly affect conformation or binding as compared with native sequences. We have examined the preparation and application of propargyloxyproline (Pop) residues as a precursor to such peptide conjugates. Pop residues are available in a range of regio- and stereoisomers from hydroxyproline precursors and are readily prepared in Fmoc-protected form. They can be incorporated routinely in peptide synthesis and broadly retain the conformational properties of the parent proline containing peptides. This is exemplified by the preparation of biotin- and fluorophore-labelled peptides derived from linear and cyclic peptides.

Molecular Recognition of Long Dicarboxylate/Dicarboxylic Species via Supramolecular/Coordinative Interactions with Ditopic Receptors. Crystal Structure of {[Cu2L(H2O)2]⊃Pimelate}(ClO4)2

1999 ◽  
Vol 38 (4) ◽  
pp. 620-621 ◽  
Author(s):  
Carla Bazzicalupi ◽  
Andrea Bencini ◽  
Antonio Bianchi ◽  
Vieri Fusi ◽  
Enrique Garcia-España ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Recognition ◽  
Ditopic Receptors

scholarly journals A substrate selected by phage display exhibits enhanced side-chain hydrogen bonding to HIV-1 protease

2018 ◽  
Vol 74 (7) ◽  
pp. 690-694 ◽  
Author(s):  
Ian W. Windsor ◽  
Ronald T. Raines
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonding ◽  
Molecular Recognition ◽  
Hydrogen Bonds ◽  
Phage Display ◽  
Directed Evolution ◽  
Side Chain ◽  
Endogenous Substrates ◽  
Hiv 1 ◽  
Additional Hydrogen

Crystal structures of inactive variants of HIV-1 protease bound to peptides have revealed how the enzyme recognizes its endogenous substrates. The best of the known substrates is, however, a nonnatural substrate that was identified by directed evolution. The crystal structure of the complex between this substrate and the D25N variant of the protease is reported at a resolution of 1.1 Å. The structure has several unprecedented features, especially the formation of additional hydrogen bonds between the enzyme and the substrate. This work expands the understanding of molecular recognition by HIV-1 protease and informs the design of new substrates and inhibitors.

Conformational studies of transition metal carbonyl complexes of 1,5-dithiacyclooctane (1,5-DTCO) and crystal structure of [ReCl(CO)3(1,5-DTCO)]

Polyhedron ◽  
1995 ◽  
Vol 14 (5) ◽  
pp. 585-597 ◽  
Author(s):  
Edward W. Abel ◽  
Keith G. Orrell ◽  
Mark C. Poole ◽  
Vladimir Šik ◽  
Michael B. Hursthouse ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Transition Metal ◽  
Metal Carbonyl ◽  
Carbonyl Complexes ◽  
Conformational Studies ◽  
Metal Carbonyl Complexes
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