scholarly journals Structural enzymology binding studies of the peptide-substrate-binding domain of human collagen prolyl 4-hydroxylase (type-II): High affinity peptides have a PxGP sequence motif

2018 ◽  
Vol 27 (9) ◽  
pp. 1692-1703 ◽  
Author(s):  
Abhinandan V. Murthy ◽  
Ramita Sulu ◽  
M. Kristian Koski ◽  
Hongmin Tu ◽  
Jothi Anantharajan ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Sequence Motif ◽  
Type Ii ◽  
Peptide Substrate ◽  
Binding Studies ◽  
High Affinity ◽  
Structural Enzymology ◽  
Human Collagen ◽  
Peptide Substrate Binding ◽  
Substrate Binding Domain

scholarly journals The Peptide-Substrate-binding Domain of Collagen Prolyl 4-Hydroxylases Is a Tetratricopeptide Repeat Domain with Functional Aromatic Residues

2004 ◽  
Vol 279 (50) ◽  
pp. 52255-52261 ◽  
Author(s):  
Mira Pekkala ◽  
Reija Hieta ◽  
Ulrich Bergmann ◽  
Kari I. Kivirikko ◽  
Rik K. Wierenga ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Binding Domain ◽  
Tetratricopeptide Repeat ◽  
Side Chains ◽  
Type I ◽  
Type Ii ◽  
Peptide Substrate ◽  
Deep Groove ◽  
Peptide Substrate Binding ◽  
Substrate Binding Domain

Collagen prolyl 4-hydroxylases catalyze the formation of 4-hydroxyproline in -X-Pro-Gly-sequences and have an essential role in collagen synthesis. The vertebrate enzymes are α2β2tetramers in which the catalytic α-subunits contain separate peptide-substrate-binding and catalytic domains. We report on the crystal structure of the peptide-substrate-binding domain of the human type I enzyme refined at 2.3 Å resolution. It was found to belong to a family of tetratricopeptide repeat domains that are involved in many protein-protein interactions and consist of five α-helices forming two tetratricopeptide repeat motifs plus the solvating helix. A prominent feature of its concave surface is a deep groove lined by tyrosines, a putative binding site for proline-rich Tripeptides. Solvent-exposed side chains of three of the tyrosines have a repeat distance similar to that of a poly-l-proline type II helix. The aromatic surface ends at one of the tyrosines, where the groove curves almost 90° away from the linear arrangement of the three tyrosine side chains, possibly inducing a bent conformation in the bound peptide. This finding is consistent with previous suggestions by others that a minimal structural requirement for proline 4-hydroxylation may be a sequence in the poly-l-proline type II conformation followed by a β-turn in the Pro-Gly segment. Site-directed mutagenesis indicated that none of the tyrosines was critical for tetramer assembly, whereas most of them were critical for the binding of a peptide substrate and inhibitor both to the domain and the α2β2enzyme tetramer.

scholarly journals The Peptide-Substrate-binding Domain of Human Collagen Prolyl 4-Hydroxylases

2003 ◽  
Vol 278 (37) ◽  
pp. 34966-34974 ◽  
Author(s):  
Reija Hieta ◽  
Liisa Kukkola ◽  
Perttu Permi ◽  
Päivi Pirilä ◽  
Kari I. Kivirikko ◽  
...  
Keyword(s):  
Substrate Binding ◽  
Binding Domain ◽  
Peptide Substrate ◽  
Human Collagen ◽  
Peptide Substrate Binding ◽  
Substrate Binding Domain

scholarly journals Unique Peptide Substrate Binding Properties of 110-kDa Heat-shock Protein (Hsp110) Determine Its Distinct Chaperone Activity

2011 ◽  
Vol 287 (8) ◽  
pp. 5661-5672 ◽  
Author(s):  
Xinping Xu ◽  
Evans Boateng Sarbeng ◽  
Christina Vorvis ◽  
Divya Prasanna Kumar ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Substrate Binding ◽  
Chaperone Activity ◽  
Peptide Substrate ◽  
Binding Properties ◽  
Unique Peptide ◽  
Peptide Substrate Binding

scholarly journals Allosteric Coupling between the Lid and Interdomain Linker in DnaK Revealed by Inhibitor Binding Studies

2008 ◽  
Vol 191 (5) ◽  
pp. 1456-1462 ◽  
Author(s):  
Markus Liebscher ◽  
Anna Roujeinikova
Keyword(s):  
Substrate Binding ◽  
Crystallographic Analysis ◽  
Peptide Inhibitors ◽  
Binding Studies ◽  
Allosteric Inhibitors ◽  
E Coli ◽  
Allosteric Coupling ◽  
Chaperone Dnak ◽  
Interdomain Linker ◽  
Substrate Binding Domain

ABSTRACT The molecular chaperone DnaK assists protein folding and refolding, translocation across membranes, and regulation of the heat shock response. In Escherichia coli, the protein is a target for insect-derived antimicrobial peptides, pyrrhocoricins. We present here the X-ray crystallographic analysis of the E. coli DnaK substrate-binding domain in complex with pyrrhocoricin-derived peptide inhibitors. The structures show that pyrrhocoricins act as site-specific, dual-mode (competitive and allosteric) inhibitors, occupying the substrate-binding tunnel and disrupting the latch between the lid and the β-sandwich. Our structural analysis revealed an allosteric coupling between the movements of the lid and the interdomain linker, identifying a previously unknown mechanism of the lid-mediated regulation of the chaperone cycle.

scholarly journals Entropic Inhibition: How the Activity of a AAA+ Machine Is Modulated by Its Substrate-Binding Domain

2021 ◽  
Author(s):  
Marija Iljina ◽  
Hisham Mazal ◽  
Pierre Goloubinoff ◽  
Inbal Riven ◽  
Gilad Haran
Keyword(s):  
Substrate Binding ◽  
Binding Domain ◽  
Substrate Binding Domain
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