scholarly journals Molecular mechanism underlying substrate recognition of the peptide macrocyclase PsnB

2021 ◽  
Author(s):  
Inseok Song ◽  
Younghyeon Kim ◽  
Jaeseung Yu ◽  
Su Yong Go ◽  
Hong Geun Lee ◽  
...  

AbstractGraspetides, also known as omega-ester-containing peptides (OEPs), are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) bearing side-to-side macrolactone or macrolactam linkages. Here we present molecular details of the precursor recognition of the macrocyclase enzyme PsnB in the biosynthesis of plesiocin, a Group 2 graspetide. Biochemical analysis revealed that, in contrast to other RiPPs, the core region of the plesiocin precursor peptide noticeably enhanced the enzyme-precursor interaction via the conserved glutamates. We obtained four crystal structures of symmetric or asymmetric PsnB dimers including those with a bound core peptide and a nucleotide, and suggest that the highly conserved Arg213 at the enzyme active site specifically recognizes a ring-forming acidic residue and escorts it to ATP for phosphorylation. Collectively, this study provides insights into the mechanism underlying substrate recognition in the graspetide biosynthesis, and lays a foundation for engineering new variants.

RSC Advances ◽  
2016 ◽  
Vol 6 (97) ◽  
pp. 94643-94650 ◽  
Author(s):  
Shuzhen Wang ◽  
Xulu Zheng ◽  
Qi Pan ◽  
Yijun Chen

Thr3 in the core peptide of NosM could be mutated to generate nosiheptide analogues retaining antimicrobial activities.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yunliang Chen ◽  
Jinxiu Wang ◽  
Guoquan Li ◽  
Yunpeng Yang ◽  
Wei Ding

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products that benefited from genome sequencing technology in the past two decades. RiPPs are widely distributed in nature and show diverse chemical structures and rich biological activities. Despite the various structural characteristic of RiPPs, they follow a common biosynthetic logic: a precursor peptide containing an N-terminal leader peptide and a C-terminal core peptide; in some cases,a follower peptide is after the core peptide. The precursor peptide undergoes a series of modification, transport, and cleavage steps to form a mature natural product with specific activities. Sactipeptides (Sulfur-to-alpha carbon thioether cross-linked peptides) belong to RiPPs that show various biological activities such as antibacterial, spermicidal and hemolytic properties. Their common hallmark is an intramolecular thioether bond that crosslinks the sulfur atom of a cysteine residue to the α-carbon of an acceptor amino acid, which is catalyzed by a rSAM enzyme. This review summarizes recent achievements concerning the discovery, distribution, structural elucidation, biosynthesis and application prospects of sactipeptides.


2019 ◽  
Author(s):  
Marcel Lagedroste ◽  
Jens Reiners ◽  
Sander H.J. Smits ◽  
Lutz Schmitt

AbstractLanthipeptides are ribosomally synthesized and post-translationally modified peptides containing dehydrated amino acids and (methyl-)lanthionine rings. One of the best-studied example is nisin, which is synthesized as a precursor peptide comprising of an N-terminal leader peptide and a C-terminal core peptide. Amongst others, the leader peptide is crucial for enzyme recognition and acts as a secretion signal for the ABC transporter NisT which secrets nisin in a proposed channeling mechanism. Here, we present an in vivo secretion analysis of this process in the presence and absence of the maturation machinery composed of the dehydratase NisB and the cyclase NisC. The data clearly demonstrated that the function of NisC, but the mere presence of NisB modulated the apparent secretion rates. Additional in vitro studies of detergent-solubilized NisT revealed how the activity of this ABC transporter is again influenced by the enzymes of the maturation machinery, but not the substrate.


Author(s):  
Philip D. Lunger ◽  
H. Fred Clark

In the course of fine structure studies of spontaneous “C-type” particle production in a viper (Vipera russelli) spleen cell line, designated VSW, virus particles were frequently observed within mitochondria. The latter were usually enlarged or swollen, compared to virus-free mitochondria, and displayed a considerable degree of cristae disorganization.Intramitochondrial viruses measure 90 to 100 mμ in diameter, and consist of a nucleoid or core region of varying density and measuring approximately 45 mμ in diameter. Nucleoid density variation is presumed to reflect varying degrees of condensation, and hence maturation stages. The core region is surrounded by a less-dense outer zone presumably representing viral capsid.Particles are usually situated in peripheral regions of the mitochondrion. In most instances they appear to be lodged between loosely apposed inner and outer mitochondrial membranes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Aftab Uddin ◽  
Shammi Akter ◽  
Mahbuba Ferdous ◽  
Badrul Haidar ◽  
Al Amin ◽  
...  

AbstractHere we report a jute endophyte Staphylococcus hominis strain MBL_AB63 isolated from jute seeds which showed promising antimicrobial activity against Staphylococcus aureus SG511 when screening for antimicrobial substances. The whole genome sequence of this strain, annotated using BAGEL4 and antiSMASH 5.0 to predict the gene clusters for antimicrobial substances identified a novel antimicrobial peptide cluster that belongs to the class I lantibiotic group. The predicted lantibiotic (homicorcin) was found to be 82% similar to a reported peptide epicidin 280 having a difference of seven amino acids at several positions of the core peptide. Two distinct peaks obtained at close retention times from a RP-HPLC purified fraction have comparable antimicrobial activities and LC–MS revealed the molecular mass of these peaks to be 3046.5 and 3043.2 Da. The presence of an oxidoreductase (homO) similar to that of epicidin 280- associated eciO or epilancin 15X- associated elxO in the homicorcin gene cluster is predicted to be responsible for the reduction of the first dehydrated residue dehydroalanine (Dha) to 2-hydroxypropionate that causes an increase of 3 Da mass of homicorcin 1. Trypsin digestion of the core peptide and its variant followed by ESI–MS analysis suggests the presence of three ring structures, one in the N-terminal and other two interlocking rings at the C-terminal region that remain undigested. Homicorcin exerts bactericidal activity against susceptible cells by disrupting the integrity of the cytoplasmic membrane through pore formation as observed under FE-SEM.


1984 ◽  
Vol 108 ◽  
pp. 257-258
Author(s):  
Michael Rosa ◽  
Jorge Melnick ◽  
Preben Grosbol

The massive H II region NGC 3603 is the closest galactic counterpart to the giant LMC nebula 30 Dor. Walborn (1973) first compared the ionizing OB/WR clusters of the two H II regions and suggested that R 136, the unresolved luminous WR + 0 type central object of 30 Dor, might be a multiple system like the core region of NGC 3603. Suggestions that the dominant component of R 136, i.e. R 136A, might be either a single or a very few supermassive and superluminous stars (Schmidt-Kaler and Feitzinger 1982, Savage et al. 1983) have recently been disputed by Moffat and Seggewiss (1983) and Melnick (1983), who have presented spectroscopic and photometric evidence to support the hypothesis of an unresolved cluster of stars. We have extended Walborn's original comparison of the apparent morphology of the two clusters by digital treatment of the images to simulate how the galactic cluster would look like if it were located in the LMC


2021 ◽  
Author(s):  
Marcela Eduarda Della Libera de Godoy ◽  
Valdir F. Novello ◽  
Francisco William Cruz

<p>South American Monsoon System (SAMS) and its main feature, the South American Convergence Zone (SACZ) are responsible for the major distribution of moisture in South America. The current work presents a novel high-resolution oxygen isotope record (δ<sup>18</sup>O) based on speleothems from southwest Amazon basin (Brazil), right at SAMS' core region and SACZ onset, where there is still a gap of high resolution paleoclimate records. The novel δ<sup>18</sup>O record presents an average of 3 year-resolution, composed by 1344 stable isotope analysis performed in two speleothems with a well-resolved chronology (37 U/Th ages) with average errors <1%. This work aims to describe the rainfall variability of the core region of the South American monsoon for the last 3k years and to take a broader look at precipitation patterns over Amazon basin. The Rondônia δ18O record shows three main stages throughout this time period. The first is from -1000 to ~400 CE, where it’s in accordance with most of other paleorecords from the Amazon basin. the second segment  is from ~400 to 1200 CE, when there is a continuous increase in the δ18O record until it reaches its highest values around 850 CE during the MCA (800-1200 CE), which is in accordance with western Amazon records, whilst the record in eastern Amazon presents an opposite trend. Thus, a precipitation dipole over Amazon emerges from ~400 CE onwards, majorly triggered by anomalous climate changes such as MCA, where western (eastern) Amazon is drier (wetter). During LIA (1450-1800 CE), on the other hand, Rondônia record presents its lowest values, also agreeing with western records and with records under the influence of SACZ whilst on eastern Amazon a drier period is established. Therefore, with this novel paleoclimate record located at the core region of SAMS, it's possible to evidence the dynamics of the precipitation dipole over the Amazon region, as well as understand the SACZ intensity variations.</p>


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