Mechanistic Analysis of a Type II Polyketide Synthase. Role of Conserved Residues in the β-Ketoacyl Synthase−Chain Length Factor Heterodimer†

Biochemistry ◽  
2000 ◽  
Vol 39 (8) ◽  
pp. 2088-2095 ◽  
Author(s):  
Juerg Dreier ◽  
Chaitan Khosla
Keyword(s):  
Chain Length ◽  
Polyketide Synthase ◽  
Type Ii ◽  
Conserved Residues ◽  
Mechanistic Analysis ◽  
Ketoacyl Synthase

scholarly journals A Novel Multidomain Polyketide Synthase Is Essential for Zeamine Production and the Virulence of Dickeya zeae

2011 ◽  
Vol 24 (10) ◽  
pp. 1156-1164 ◽  
Author(s):  
Jianuan Zhou ◽  
Haibao Zhang ◽  
Jien Wu ◽  
Qiongguang Liu ◽  
Pinggen Xi ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Mechanisms ◽  
Polyketide Synthase ◽  
Acyl Carrier Protein ◽  
Multidomain Structure ◽  
Ketoacyl Synthase ◽  
Rot Disease ◽  
Alignment Analysis ◽  
The Relationship

Dickeya zeae is the causal agent of the rice foot rot disease, but its mechanism of infection remains largely unknown. In this study, we identified and characterized a novel gene designated as zmsA. The gene encodes a large protein of 2,346 amino acids in length, which consists of multidomains arranged in the order of N-terminus, β-ketoacyl synthase, acyl transferase, acyl carrier protein, β-ketoacyl reductase, dehydratase. This multidomain structure and sequence alignment analysis suggest that ZmsA is a member of the polyketide synthase family. Mutation of zmsA abolished antimicrobial activity and attenuated the virulence of D. zeae. To determine the relationship between antimicrobial activity and virulence, active compounds were purified from D. zeae EC1 and were structurally characterized. This led to identification of two polyamino compounds, i.e., zeamine and zeamine II, that were phytotoxins and potent antibiotics. These results have established the essential role of ZmsA in zeamine biosynthesis and presented a new insight on the molecular mechanisms of D. zeae pathogenicity.

Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics

Diabetes ◽  
1987 ◽  
Vol 36 (3) ◽  
pp. 274-283 ◽  
Author(s):  
A. D. Baron ◽  
L. Schaeffer ◽  
P. Shragg ◽  
O. G. Kolterman
Keyword(s):  
Type Ii ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Type Ii Diabetics ◽  
Glucose Output

Role of lipid oxidation in pathogenesis of insulin resistance of obesity and type II diabetes

Diabetes ◽  
1987 ◽  
Vol 36 (11) ◽  
pp. 1341-1350 ◽  
Author(s):  
J. P. Felber ◽  
E. Ferrannini ◽  
A. Golay ◽  
H. U. Meyer ◽  
D. Theibaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Oxidation ◽  
Type Ii Diabetes ◽  
Type Ii

Directive Effect of Chain Length in Modulating Peptide Nano-assemblies

2020 ◽  
Vol 27 (9) ◽  
pp. 923-929
Author(s):  
Gaurav Pandey ◽  
Prem Prakash Das ◽  
Vibin Ramakrishnan
Keyword(s):  
Electron Microscopy ◽  
Amino Acids ◽  
Light Scattering ◽  
Chain Length ◽  
Self Assembly ◽  
The Self ◽  
Ionic Charge ◽  
Self Assembling ◽  
Biophysical Techniques

Background: RADA-4 (Ac-RADARADARADARADA-NH2) is the most extensively studied and marketed self-assembling peptide, forming hydrogel, used to create defined threedimensional microenvironments for cell culture applications. Objectives: In this work, we use various biophysical techniques to investigate the length dependency of RADA aggregation and assembly. Methods: We synthesized a series of RADA-N peptides, N ranging from 1 to 4, resulting in four peptides having 4, 8, 12, and 16 amino acids in their sequence. Through a combination of various biophysical methods including thioflavin T fluorescence assay, static right angle light scattering assay, Dynamic Light Scattering (DLS), electron microscopy, CD, and IR spectroscopy, we have examined the role of chain-length on the self-assembly of RADA peptide. Results: Our observations show that the aggregation of ionic, charge-complementary RADA motifcontaining peptides is length-dependent, with N less than 3 are not forming spontaneous selfassemblies. Conclusion: The six biophysical experiments discussed in this paper validate the significance of chain-length on the epitaxial growth of RADA peptide self-assembly.

scholarly journals PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Dawei Chen ◽  
Zhenguo Zhao ◽  
Lu Chen ◽  
Qinghua Li ◽  
Jixue Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Alternative Splicing ◽  
Protein Function ◽  
Vital Role ◽  
Normal Tissues ◽  
Mechanistic Analysis ◽  
Highly Correlated ◽  
Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

scholarly journals Transcriptome Changes in Pseudomonas putida KT2440 during Medium-Chain-Length Polyhydroxyalkanoate Synthesis Induced by Nitrogen Limitation

2020 ◽  
Vol 22 (1) ◽  
pp. 152
Author(s):  
Dorota Dabrowska ◽  
Justyna Mozejko-Ciesielska ◽  
Tomasz Pokój ◽  
Slawomir Ciesielski
Keyword(s):  
Chain Length ◽  
Nitrogen Limitation ◽  
Stringent Response ◽  
Wild Type ◽  
Pseudomonas Putida Kt2440 ◽  
Medium Chain ◽  
Environmental Stimuli ◽  
Medium Chain Length ◽  
In The Wild

Pseudomonas putida’s versatility and metabolic flexibility make it an ideal biotechnological platform for producing valuable chemicals, such as medium-chain-length polyhydroxyalkanoates (mcl-PHAs), which are considered the next generation bioplastics. This bacterium responds to environmental stimuli by rearranging its metabolism to improve its fitness and increase its chances of survival in harsh environments. Mcl-PHAs play an important role in central metabolism, serving as a reservoir of carbon and energy. Due to the complexity of mcl-PHAs’ metabolism, the manner in which P. putida changes its transcriptome to favor mcl-PHA synthesis in response to environmental stimuli remains unclear. Therefore, our objective was to investigate how the P. putida KT2440 wild type and mutants adjust their transcriptomes to synthesize mcl-PHAs in response to nitrogen limitation when supplied with sodium gluconate as an external carbon source. We found that, under nitrogen limitation, mcl-PHA accumulation is significantly lower in the mutant deficient in the stringent response than in the wild type or the rpoN mutant. Transcriptome analysis revealed that, under N-limiting conditions, 24 genes were downregulated and 21 were upregulated that were common to all three strains. Additionally, potential regulators of these genes were identified: the global anaerobic regulator (Anr, consisting of FnrA, Fnrb, and FnrC), NorR, NasT, the sigma54-dependent transcriptional regulator, and the dual component NtrB/NtrC regulator all appear to play important roles in transcriptome rearrangement under N-limiting conditions. The role of these regulators in mcl-PHA synthesis is discussed.

scholarly journals Polyketide Double Bond Biosynthesis. Mechanistic Analysis of the Dehydratase-Containing Module 2 of the Picromycin/Methymycin Polyketide Synthase

2005 ◽  
Vol 127 (49) ◽  
pp. 17393-17404 ◽  
Author(s):  
Jiaquan Wu ◽  
Toby J. Zaleski ◽  
Chiara Valenzano ◽  
Chaitan Khosla ◽  
David E. Cane
Keyword(s):  
Double Bond ◽  
Polyketide Synthase ◽  
Mechanistic Analysis

The Role of Conserved Residues in the DEDDh Motif: the Proton-Transfer Mechanism of HIV-1 RNase H

ACS Catalysis ◽  
2021 ◽  
pp. 7915-7927
Author(s):  
Simon L. Dürr ◽  
Olga Bohuszewicz ◽  
Dénes Berta ◽  
Reynier Suardiaz ◽  
Pablo G. Jambrina ◽  
...  
Keyword(s):  
Proton Transfer ◽  
Rnase H ◽  
Transfer Mechanism ◽  
Conserved Residues ◽  
Hiv 1
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