scholarly journals Identification of active sites in amidase: Evolutionary relationship between amide bond- and peptide bond-cleaving enzymes

1997 ◽  
Vol 94 (22) ◽  
pp. 11986-11991 ◽  
Author(s):  
M. Kobayashi ◽  
Y. Fujiwara ◽  
M. Goda ◽  
H. Komeda ◽  
S. Shimizu
Keyword(s):  
Active Sites ◽  
Evolutionary Relationship ◽  
Peptide Bond ◽  
Amide Bond

scholarly journals A Zirconium Metal-Organic Framework with SOC Topological Net for Catalytic Peptide Bond Hydrolysis

2021 ◽  
Author(s):  
Sujing Wang ◽  
Antoine Tissot ◽  
Guillaume Maurin ◽  
Tatjana Parac-Vogt ◽  
Christian Serre ◽  
...  
Keyword(s):  
Active Sites ◽  
Metal Organic Framework ◽  
Cost Effective ◽  
Peptide Bond ◽  
Catalytic Performance ◽  
Wide Range ◽  
Horse Heart Myoglobin ◽  
Metal Organic ◽  
Effective Synthesis ◽  
Organic Framework

<div>The discovery of nanozymes for selective cleavage of proteins would boost the emerging areas of modern proteomics, however, the development of efficient and reusable artificial catalysts for peptide bond hydrolysis is challenging. Here we report the detailed catalytic properties of a microporous zirconium carboxylate metal-organic framework, MIP-201, in promoting peptide bond hydrolysis in a simple dipeptide, as well as in horse-heart myoglobin (Mb) protein that consists of 153 amino acids. We demonstrate that MIP-201 features an excellent catalytic activity and selectivity, a good tolerance toward reaction conditions covering a wide range of different pH values, and importantly, an exceptional recycling ability associated with easy regeneration process. Taking into account the excellent catalytic performance of MIP-201 and its other advantages such as 6-connected Zr6 cluster active sites, the green, scalable and cost-effective synthesis, and an outstanding chemical and architectural stability, our finding suggests that MIP-201 may be a promising and practical alternative to the current commercially available catalysts for peptide bond hydrolysis.</div>

scholarly journals A Zirconium Metal-Organic Framework with SOC Topological Net for Catalytic Peptide Bond Hydrolysis

2021 ◽  
Author(s):  
Sujing Wang ◽  
Antoine Tissot ◽  
Guillaume Maurin ◽  
Tatjana Parac-Vogt ◽  
Christian Serre ◽  
...  
Keyword(s):  
Active Sites ◽  
Metal Organic Framework ◽  
Cost Effective ◽  
Peptide Bond ◽  
Catalytic Performance ◽  
Wide Range ◽  
Horse Heart Myoglobin ◽  
Metal Organic ◽  
Effective Synthesis ◽  
Organic Framework

<div>The discovery of nanozymes for selective cleavage of proteins would boost the emerging areas of modern proteomics, however, the development of efficient and reusable artificial catalysts for peptide bond hydrolysis is challenging. Here we report the detailed catalytic properties of a microporous zirconium carboxylate metal-organic framework, MIP-201, in promoting peptide bond hydrolysis in a simple dipeptide, as well as in horse-heart myoglobin (Mb) protein that consists of 153 amino acids. We demonstrate that MIP-201 features an excellent catalytic activity and selectivity, a good tolerance toward reaction conditions covering a wide range of different pH values, and importantly, an exceptional recycling ability associated with easy regeneration process. Taking into account the excellent catalytic performance of MIP-201 and its other advantages such as 6-connected Zr6 cluster active sites, the green, scalable and cost-effective synthesis, and an outstanding chemical and architectural stability, our finding suggests that MIP-201 may be a promising and practical alternative to the current commercially available catalysts for peptide bond hydrolysis.</div>

The protease MBTPS2 is an important regulator of several cellular processes, especially in health and sickness

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Active Sites ◽  
Peptide Bond ◽  
Cellular Processes ◽  
Disease States ◽  
Tremendous Progress ◽  
Catalytic Sites ◽  
Important Regulator ◽  
Catalytic Active Sites ◽  
Proteolytic Action ◽  
Health And Sickness

Since the identification of MBTPS2 in 1997, tremendous progress has been made in determining the protease's functions. The protease has developed from an element of the SREBP cleavage machinery to an important regulator of several cellular processes, especially in health and sickness. With this newfound information from biochemical and structural biology, S2P's proteolytic action through peptide bond hydrolysis can occur in the membrane, providing a conceptual framework for appreciating S2P's roles in other aspects, and showing that many other substrates rely on S2P for their survival. In addition, we discovered the identity of both of S2P's catalytic active sites, an essential finding as the activity of the proteolysis as well as the pathogenesis of MBTPS2-caused illnesses seems to be connected to the molecular and biochemical features of the catalytic sites. Additionally, MBTPS2 causes different diseases, possibly illustrating the pleiotropic nature of the protein. Also, while the ailments reported thus far are all due to mutations that cause MBTPS2 to lose function, other variants that cause MBTPS2 to be hyperactive have not been examined. Nevertheless, recognizing the related sickness pathomechanism is a challenge. Pursuing these challenging technical areas would most definitely enhance our understanding of MBTPS2 in disease states. MBTPS2 appears to be nearing the solution to many of the remaining fundamental questions surrounding the mechanism of its action, as well as being a therapeutic target for new therapies.

Understanding condensation domain selectivity in non-ribosomal peptide biosynthesis: structural characterization of the acceptor bound state

2021 ◽  
Author(s):  
Max Cryle ◽  
Thierry Izore ◽  
Y. T. Ho ◽  
Joe Kaczmarski ◽  
Athina Gavriilidou ◽  
...  
Keyword(s):  
Active Site ◽  
Active Sites ◽  
Peptide Bond ◽  
Bound State ◽  
Modular Assembly ◽  
Central Function ◽  
Acceptor Substrate ◽  
Peptide Synthetases ◽  
Peptide Biosynthesis ◽  
Condensation Domain

Abstract Non-ribosomal peptide synthetases are important enzymes for the assembly of complex peptide natural products. Within these multi-modular assembly lines, condensation domains perform the central function of chain assembly, typically by forming a peptide bond between two peptidyl carrier protein (PCP)-bound substrates. In this work, we report the first structural snapshots of a condensation domain in complex with an aminoacyl-PCP acceptor substrate. These structures allow the identification of a mechanism that controls access of acceptor substrates to the active site in condensation domains. The structures of this previously uncharacterized complex also allow us to demonstrate that condensation domain active sites do not contain a distinct pocket to select the side chain of the acceptor substrate during peptide assembly but that residues within the active site motif can instead serve to tune the selectivity of these central biosynthetic domains.

scholarly journals CF2H as a hydrogen bond donor group for the fine tuning of peptide bond geometry with difluoromethylated pseudoprolines

2019 ◽  
Vol 55 (83) ◽  
pp. 12487-12490 ◽  
Author(s):  
N. Malquin ◽  
K. Rahgoshay ◽  
N. Lensen ◽  
G. Chaume ◽  
E. Miclet ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Peptide Bond ◽  
Fine Tuning ◽  
Amide Bond ◽  
Donor Group ◽  
Hydrogen Bond Donor

CF2H-Pseudoprolines obtained from difluoroacetaldehyde hemiacetal and serine are stable proline surrogates. An intramolecular H-bond due to the CF2H group is promoting an exceptionally high content of cis-amide bond conformation.

scholarly journals Crystal structure of highly glycosylated human leukocyte elastase in complex with an S2′ site binding inhibitor

2018 ◽  
Vol 74 (8) ◽  
pp. 480-489 ◽  
Author(s):  
Jennifer Hochscherf ◽  
Markus Pietsch ◽  
William Tieu ◽  
Kevin Kuan ◽  
Andrew D. Abell ◽  
...  
Keyword(s):  
Active Sites ◽  
Crystal Packing ◽  
Human Leukocyte ◽  
Peptide Bond ◽  
Side Chain ◽  
Leukocyte Elastase ◽  
Substrate Protein ◽  
Human Leukocyte Elastase ◽  
Crystalline Environment ◽  
Site Binding

Glycosylated human leukocyte elastase (HLE) was crystallized and structurally analysed in complex with a 1,3-thiazolidine-2,4-dione derivative that had been identified as an HLE inhibitor in preliminary studies. In contrast to previously described HLE structures with small-molecule inhibitors, in this structure the inhibitor does not bind to the S1 and S2 substrate-recognition sites; rather, this is the first HLE structure with a synthetic inhibitor in which the S2′ site is blocked that normally binds the second side chain at the C-terminal side of the scissile peptide bond in a substrate protein. The inhibitor also induces the formation of crystalline HLE dimers that block access to the active sites and that are also predicted to be stable in solution. Neither such HLE dimers nor the corresponding crystal packing have been observed in previous HLE crystal structures. This novel crystalline environment contributes to the observation that comparatively large parts of the N-glycan chains of HLE are defined by electron density. The final HLE structure contains the largest structurally defined carbohydrate trees among currently available HLE structures.

scholarly journals Structural evidence for a proline-specific glycopeptide recognition domain in an O-glycopeptidase

Glycobiology ◽  
2020 ◽  
Author(s):  
Ilit Noach ◽  
Alisdair B Boraston
Keyword(s):  
Active Sites ◽  
Substrate Recognition ◽  
Peptide Bond ◽  
Multidomain Protein ◽  
Threonine Residue ◽  
Tyrosine Residues ◽  
Host Pathogen Interaction ◽  
A Site ◽  
Insight Into

Abstract The glycosylation of proteins is typically considered as a stabilizing modification, including resistance to proteolysis. A class of peptidases, referred to as glycopeptidases or O-glycopeptidases, circumvent the protective effect of glycans against proteolysis by accommodating the glycans in their active sites as specific features of substrate recognition. IMPa from Pseudomonas aeruginosa is such an O-glycopeptidase that cleaves the peptide bond immediately preceding a site of O-glycosylation, and through this glycoprotein-degrading function contributes to the host-pathogen interaction. IMPa, however, is a relatively large multidomain protein and how its additional domains may contribute to its function remains unknown. Here, through the determination of a crystal structure of IMPa in complex with an O-glycopeptide, we reveal that the N-terminal domain of IMPa, which is classified in Pfam as IMPa_N_2, is a proline recognition domain that also shows the properties of recognizing an O-linked glycan on the serine/threonine residue following the proline. The proline is bound in the center of a bowl formed by four functionally conserved aromatic amino acid side chains while the glycan wraps around one of the tyrosine residues in the bowl to make classic aromatic ring-carbohydrate CH-π interactions. This structural evidence provides unprecedented insight into how the ancillary domains in glycoprotein-specific peptidases can noncatalytically recognize specific glycosylated motifs that are common in mucin and mucin-like molecules.

scholarly journals Unwanted hydrolysis or α/β-peptide bond formation: how long should the rate-limiting coupling step take?

RSC Advances ◽  
2019 ◽  
Vol 9 (53) ◽  
pp. 30720-30728 ◽  
Author(s):  
Viktória Goldschmidt Gőz ◽  
Adrienn Nagy ◽  
Viktor Farkas ◽  
Ernő Keszei ◽  
András Perczel
Keyword(s):  
Amino Acids ◽  
Bond Formation ◽  
Side Reaction ◽  
Peptide Bond ◽  
Amide Bond ◽  
Peptide Bond Formation ◽  
Active Esters ◽  
Amide Bond Formation ◽  
Rate Limiting ◽  
Hydrolysis Of

Parallel to the amide bond formation, the hydrolysis of the active esters of α/β-amino acids, as an unwanted side reaction limiting coupling efficacy, is studied.

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