Home About us Contact
|
Home About us Contact | ||
|
|
||
Peptide Bond Formation (peptide + bond_formation)
Selected AbstractsCover Picture: The Proto-Ribosome: An Ancient Nano-machine for Peptide Bond Formation (Isr. J. Chem.ISRAEL JOURNAL OF CHEMISTRY, Issue 1 20101/2010) The cover picture shows the ribosome 50S subunit on a fungal background. Represented fungi, Clitopilus scyphoides, produce antibiotics of the pleuromutilin family. Pleuromutilins ,moving" into the ribosome Peptidyl Binding Centre (PTC) are also shown. The figure was contributed by Anat Bashan and Ada Yonath (see The Proto-Ribosome: An Ancient Nano-machine for Peptide Bond Formation, Davidovich et al., p. 29 in this issue). [source] Ribosomal crystallography: Peptide bond formation and its inhibitionBIOPOLYMERS, Issue 1 2003Anat Bashan Abstract Ribosomes, the universal cellular organelles catalyzing the translation of genetic code into proteins, are protein/RNA assemblies, of a molecular weight 2.5 mega Daltons or higher. They are built of two subunits that associate for performing protein biosynthesis. The large subunit creates the peptide bond and provides the path for emerging proteins. The small has key roles in initiating the process and controlling its fidelity. Crystallographic studies on complexes of the small and the large eubacterial ribosomal subunits with substrate analogs, antibiotics, and inhibitors confirmed that the ribosomal RNA governs most of its activities, and indicated that the main catalytic contribution of the ribosome is the precise positioning and alignment of its substrates, the tRNA molecules. A symmetry-related region of a significant size, containing about two hundred nucleotides, was revealed in all known structures of the large ribosomal subunit, despite the asymmetric nature of the ribosome. The symmetry rotation axis, identified in the middle of the peptide-bond formation site, coincides with the bond connecting the tRNA double-helical features with its single-stranded 3, end, which is the moiety carrying the amino acids. This thus implies sovereign movements of tRNA features and suggests that tRNA translocation involves a rotatory motion within the ribosomal active site. This motion is guided and anchored by ribosomal nucleotides belonging to the active site walls, and results in geometry suitable for peptide-bond formation with no significant rearrangements. The sole geometrical requirement for this proposed mechanism is that the initial P-site tRNA adopts the flipped orientation. The rotatory motion is the major component of unified machinery for peptide-bond formation, translocation, and nascent protein progression, since its spiral nature ensures the entrance of the nascent peptide into the ribosomal exit tunnel. This tunnel, assumed to be a passive path for the growing chains, was found to be involved dynamically in gating and discrimination. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003 [source] Phylogenetic analysis of condensation domains in the nonribosomal peptide synthetasesFEMS MICROBIOLOGY LETTERS, Issue 1 2005Niran Roongsawang Abstract Condensation (C) domains in the nonribosomal peptide synthetases are capable of catalyzing peptide bond formation between two consecutively bound various amino acids. C-domains coincide in frequency with the number of peptide bonds in the product peptide. In this study, a phylogenetic approach was used to investigate structural diversity of bacterial C-domains. Phylogenetic trees show that the C-domains are clustered into three functional groups according to the types of substrate donor molecules. They are l -peptidyl donors, d -peptidyl donors, and N -acyl donors. The fact that C-domain structure is not subject to optical configuration of amino acid acceptor molecules supports an idea that the conversion from l to d -form of incorporating amino acid acceptor occurs during or after peptide bond formation. l -peptidyl donors and d -peptidyl donors are suggested to separate before separating the lineage of Gram-positive and Gram-negative bacteria in the evolution process. [source] The expansion of mechanistic and organismic diversity associated with non-ribosomal peptidesFEMS MICROBIOLOGY LETTERS, Issue 2 2000Michelle C Moffitt Abstract Non-ribosomal peptides are a group of secondary metabolites with a wide range of bioactivities, produced by prokaryotes and lower eukaryotes. Recently, non-ribosomal synthesis has been detected in diverse microorganisms, including the myxobacteria and cyanobacteria. Peptides biosynthesized non-ribosomally may often play a primary or secondary role in the producing organism. Non-ribosomal peptides are often small in size and contain unusual or modified amino acids. Biosynthesis occurs via large modular enzyme complexes, with each module responsible for the activation and thiolation of each amino acid, followed by peptide bond formation between activated amino acids. Modules may also be responsible for the enzymatic modification of the substrate amino acid. Recent analysis of biosynthetic gene clusters has identified novel integrated, mixed and hybrid enzyme systems. These diverse mechanisms of biosynthesis result in the wide variety of non-ribosomal peptide structures and bioactivities seen today. Knowledge of these biosynthetic systems is rapidly increasing and methods of genetically engineering these systems are being developed. In the future, this may lead to rational drug design through combinatorial biosynthesis of these enzyme systems. [source] Catechol as a nucleophilic catalyst of peptide bond formationJOURNAL OF PEPTIDE SCIENCE, Issue 1 2002Gabriela Ivanova Abstract The aminolysis of a mildly activated aminoacid ester, benzyloxycarbonyl- L -phenylalanine cyanomethyl ester, by glycine esters in the presence of catechol has been studied as a model of catalysis by RNA cis -vicinal-diol systems in protein biosynthesis. Catechol accelerated the aminolysis, especially in the presence of bases, probably by nucleophilic catalysis. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Functional aspects of ribosomal architecture: symmetry, chirality and regulationJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2004Raz Zarivach Abstract High-resolution structures of both ribosomal subunits revealed that most stages of protein biosynthesis, including decoding of genetic information, are navigated and controlled by the elaborate ribosomal architectural-design. Remote interactions govern accurate substrate alignment within a flexible active-site pocket [peptidyl transferase center (PTC)], and spatial considerations, due mainly to a universal mobile nucleotide, U2585, ensure proper chirality by interfering with D -amino-acids incorporation. tRNA translocation involves two correlated motions: overall mRNA/tRNA (messenger and transfer RNA) shift, and a rotation of the tRNA single-stranded aminoacylated-3, end around the bond connecting it with the tRNA helical-regions. This bond coincides with an axis passing through a sizable symmetry-related region, identified around the PTC in all large-subunit crystal structures. Propelled by a bulged universal nucleotide, A2602, positioned at the two-fold symmetry axis, and guided by a ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry optimal for peptide-bond formation and in geometry ensuring nascent proteins entrance into their exit tunnel. Hence, confirming that ribosomes contribute positional rather than chemical catalysis, and that peptide bond formation is concurrent with A- to P-site tRNA passage. Connecting between the PTC, the decoding center, the tRNA entrance and exit points, the symmetry-related region can transfer intra-ribosomal signals between remote functional locations, guaranteeing smooth processivity of amino acids polymerization. Ribosomal proteins are involved in accurate substrate placement (L16), discrimination and signal transmission (L22) and protein biosynthesis regulation (CTC). Residing on the exit tunnel walls near its entrance, and stretching to its opening, protein-L22 can mediate ribosome response to cellular regulatory signals, since it can swing across the tunnel, causing gating and elongation arrest. Each of the protein CTC domains has a defined task. The N -terminal domain stabilizes the intersubunit-bridge confining the A-site-tRNA entrance. The middle domain protects the bridge conformation at elevated temperatures. The C -terminal domain can undergo substantial conformational rearrangements upon substrate binding, indicating CTC participation in biosynthesis-control under stressful conditions. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||