scholarly journals Quantifying the Relationship between Conformational Dynamics and Enzymatic Activity in Ribonuclease HI Homologues

Biochemistry ◽  
2020 ◽  
Vol 59 (35) ◽  
pp. 3201-3205
Author(s):  
James A. Martin ◽  
Paul Robustelli ◽  
Arthur G. Palmer
Keyword(s):  
Enzymatic Activity ◽  
Conformational Dynamics ◽  
The Relationship

scholarly journals Pervasive cooperative mutational effects on multiple catalytic enzyme traits emerge via long-range conformational dynamics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carlos G. Acevedo-Rocha ◽  
Aitao Li ◽  
Lorenzo D’Amore ◽  
Sabrina Hoebenreich ◽  
Joaquin Sanchis ◽  
...  
Keyword(s):  
Long Range ◽  
Fitness Landscape ◽  
Conformational Dynamics ◽  
P450 Monooxygenase ◽  
Access Channel ◽  
Long Range Interactions ◽  
Limited Protein ◽  
Dynamics Simulations ◽  
The Relationship ◽  
Single Enzyme

AbstractMultidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. To date, such efforts usually focus on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report a multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We develop a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative signs and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and β-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers insights for engineering P450s.

scholarly journals LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect

2018 ◽  
Vol 115 (7) ◽  
pp. E1465-E1474 ◽  
Author(s):  
Shaoxun Xiang ◽  
Hao Gu ◽  
Lei Jin ◽  
Rick F. Thorne ◽  
Xu Dong Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Enzymatic Activity ◽  
Cancer Cells ◽  
Long Noncoding Rna ◽  
Warburg Effect ◽  
Noncoding Rna ◽  
Ros Production ◽  
Xenograft Growth ◽  
The Relationship ◽  
The Warburg Effect

The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1α, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two major regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1α in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased α-KG and decreased ROS production and subsequent HIF1α down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1α. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment.

L-SERINE DEHYDRATASE (DEAMINASE) OF PSYCHROPHILES AND MESOPHILES FROM POLAR AND TEMPERATE HABITATS

1967 ◽  
Vol 13 (10) ◽  
pp. 1333-1342 ◽  
Author(s):  
James T. Staley ◽  
William L. Boyd
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Enzymatic Activity ◽  
Growth Temperature ◽  
Enzymic Activity ◽  
Direct Role ◽  
Natural Plant ◽  
Serine Dehydratase ◽  
The Relationship ◽  
Dehydratase Activity

Escherichia coli and Pseudomonas aeruginosa were grown at several temperatures ranging from 0° to 37 °C and assayed at each temperature for L-serine dehydratase activity. The relationship between enzymatic activity and growth temperature is quite different for the mesophile and psychrophile. In addition, the stimulatory effect of natural plant lecithin upon serine deamination was different for each organism, suggesting that there is either a difference in permeability or that this substance has a more direct role in enzymic activity. Also included are data confirming the results of other workers.

scholarly journals STUDIES ON THE MECHANISM OF EXPERIMENTAL PROTEINURIA INDUCED BY RENIN

1964 ◽  
Vol 120 (4) ◽  
pp. 677-690 ◽  
Author(s):  
Sharad D. Deodhar ◽  
Francis E. Cuppage ◽  
E. Gableman
Keyword(s):  
Enzymatic Activity ◽  
Adrenal Glands ◽  
Electron Microscopic ◽  
Chemically Modified ◽  
Glomerular Capillary ◽  
Enzymatic Action ◽  
Microscopic Studies ◽  
Inactive Renin ◽  
The Relationship ◽  
Permissive Role

Renin-induced proteinuria in the rat was investigated, with special emphasis on the relationship between the enzymatic activity and the proteinuric effect of renin. The dependence of the proteinuric effect on the enzymatic activity was shown by using (a) renin preparations of widely varying purity and (b) chemically modified "active" and "inactive" renin derivatives. Angiotensin II, the pressor product of the enzymatic action of renin, also produced significant proteinuria. Adrenalectomy abolished the proteinuria induced by renin. Proteinuria, however, occurred as a result of pretreatment with DOCA, or aldosterone, or without treatment, 7 to 8 weeks after adrenalectomy. Electron microscopic studies of the kidney at the time of maximal proteinuria showed focal flattening and fusion of epithelial foot processes, as well as swelling and vesicle formation in endothelial and epithelial cells of the glomeruli. Studies with intravenously injected saccharated iron oxide showed increased permeability of the glomerular capillary basement membrane to these particles. These changes were transient and were not seen 24 hours after renin injection. Adrenalectomy prevented these changes. It is concluded that renin, acting through angiotensin, causes glomerular capillary damage with increased permeability of these structures to protein and resultant proteinuria. The adrenal glands participate in a permissive role in this phenomenon.

Conformational Dynamics at the Active Site of α-Chymotrypsin and Enzymatic Activity

Langmuir ◽  
2008 ◽  
Vol 24 (15) ◽  
pp. 8163-8168 ◽  
Author(s):  
Debapriya Banerjee ◽  
Samir Kumar Pal
Keyword(s):  
Enzymatic Activity ◽  
Active Site ◽  
Conformational Dynamics

scholarly journals Pervasive cooperative mutational effects on multiple catalytic enzyme traits emerge via long-range conformational dynamics

2020 ◽  
Author(s):  
Carlos G. Acevedo-Rocha ◽  
Aitao Li ◽  
Lorenzo D’Amore ◽  
Sabrina Hoebenreich ◽  
Joaquin Sanchis ◽  
...  
Keyword(s):  
Long Range ◽  
Fitness Landscape ◽  
Conformational Dynamics ◽  
P450 Monooxygenase ◽  
Access Channel ◽  
Long Range Interactions ◽  
Limited Protein ◽  
Dynamics Simulations ◽  
The Relationship ◽  
Single Enzyme

AbstractMultidimensional fitness landscapes provide insights into the molecular basis of laboratory and natural evolution. Yet such efforts are rare and focus only on limited protein families and a single enzyme trait, with little concern about the relationship between protein epistasis and conformational dynamics. Here, we report the first multiparametric fitness landscape for a cytochrome P450 monooxygenase that was engineered for the regio- and stereoselective hydroxylation of a steroid. We developed a computational program to automatically quantify non-additive effects among all possible mutational pathways, finding pervasive cooperative sign and magnitude epistasis on multiple catalytic traits. By using quantum mechanics and molecular dynamics simulations, we show that these effects are modulated by long-range interactions in loops, helices and beta-strands that gate the substrate access channel allowing for optimal catalysis. Our work highlights the importance of conformational dynamics on epistasis in an enzyme involved in secondary metabolism and offers lessons for engineering P450s.

scholarly journals Malassezia pachydermatis: enzymes production in isolates from external ear canal of dogs with and without otitis

2005 ◽  
Vol 57 (suppl 2) ◽  
pp. 149-153 ◽  
Author(s):  
S.D.A. Coutinho
Keyword(s):  
Statistical Analysis ◽  
Enzymatic Activity ◽  
Virulence Factors ◽  
External Ear ◽  
Ear Canal ◽  
Malassezia Pachydermatis ◽  
Normal Microbiota ◽  
Ether Solution ◽  
High Production ◽  
The Relationship

The relationship between production of enzymes and pathogenicity of Malassezia pachydermatis strains was studied. Thirty strains of M. pachydermatis isolated from dogs were used: 15 originating from animals with external otitis and 15 obtained from ears of asymptomatic dogs. The samples, obtained by introduction of a sterile swab into the auditory canal after cleaning the auricle with alcohol-ether solution, were seeded onto Sabouraud dextrose agar with chloramphenicol (100mg/l) and were incubated at 37°C for up to two weeks. The colonies were identified according to their macro-and-micromorphology. All strains were investigated for the production of chondroitin-sulphatase, hyaluronidase, phospholipase and proteinase. Most of the strains showed a high production of the four enzymes. Statistical analysis did not show any differences in the enzymatic activity among the strains. M. pachydermatis originating in normal microbiota as well as in otic secretion from dogs with otitis could produce the four researched enzymes. Probably M. pachydermatis has other virulence factors that are involved in the parasitism.

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