Contribution of the FAD binding site residue tyrosine 308 to the stability of pea ferredoxin-NADP+ oxidoreductase

Biochemistry ◽  
1995 ◽  
Vol 34 (39) ◽  
pp. 12842-12848 ◽  
Author(s):  
Nora B. Calcaterra ◽  
Guillermo A. Pico ◽  
Elena G. Orellano ◽  
Jorgelina Ottado ◽  
Nestor Carrillo ◽  
...  
Keyword(s):  
Binding Site ◽  
The Stability ◽  
Fad Binding

scholarly journals Novel dynamic residue network analysis approaches to study homodimeric allosteric modulation in SARS-CoV-2 Mpro and in its evolutionary mutations

2021 ◽  
Author(s):  
Olivier Sheik Amamuddy ◽  
Rita Afriyie Baoteng ◽  
Victor Barozi ◽  
Dorothy Wavinya Nyamai ◽  
Ozlem Tastan Bishop
Keyword(s):  
Binding Site ◽  
Laboratory Strain ◽  
Allosteric Modulators ◽  
Allosteric Communication ◽  
Katz Centrality ◽  
Symmetry Problem ◽  
The Stability ◽  
Allosteric Mechanisms ◽  
Domain I ◽  
Communication Path

The rational search for allosteric modulators and the allosteric mechanisms of these modulators in the presence of evolutionary mutations, including resistant ones, is a relatively unexplored field. Here, we established novel in silico approaches and applied to SARS-CoV-2 main protease (Mpro). First, we identified six potential allosteric modulators (SANC00302, SANC00303, SANC00467, SANC00468, SANC00469, SANC00630) from the South African Natural Compounds Database (SANCDB) bound to the allosteric pocket of Mpro that we determined in our previous work. We also checked the stability of these compounds against Mpro of laboratory strain HCoV-OC43 and identified differences due to residue changes between the two proteins. Next, we focused on understanding the allosteric effects of these modulators on each protomer of the reference Mpro protein, while incorporating the symmetry problem in the functional homodimer. In general, asymmetric behavior of multimeric proteins is not commonly considered in computational analysis. We introduced a novel combinatorial approach and dynamic residue network (DRN) analysis algorithms to examine patterns of change and conservation of critical nodes, according to five independent criteria of network centrality (betweenness centrality (BC), closeness centrality (CC), degree centrality (DC), eigencentrality (EC) and katz centrality (KC)). The relationships and effectiveness of each metric in characterizing allosteric behavior were also investigated. We observed highly conserved network hubs for each averaged DRN metric on the basis of their existence in both protomers in the absence and presence of all ligands, and we called them persistent hubs (residues 17, 111, 112 and 128 for averaged BC; 6, 7, 113, 114, 115, 124, 125, 126, 127 and 128 for averaged CC; 36, 91, 146, 150 and 206 for averaged DC; 7, 115 and 125 for EC; 36, 125 and 146 for KC). We also detected ligand specific signal changes some of which were in or around functional residues (i.e. chameleon switch PHE140). Using EC persistent hubs and ligand introduced hubs we identified a residue communication path between allosteric binding site and catalytic site. Finally, we examined the effects of the mutations on the behavior of the protein in the presence of selected potential allosteric modulators and investigated the ligand stability. The hit compounds showed various levels of stability in the presence of SARS-CoV-2 Mpro mutations, being most stable in A173V, N274D and R279C, and least stable in R60C, N151D V157I, C160S and A255V. SANC00468 was the most stable compound in the 43 mutant protein systems. We further used DRN metric analysis to define cold spots as being those regions that are least impacted, or not impacted, by mutations. One crucial outcome of this study was to show that EC centrality hubs form an allosteric communication path between the allosteric ligand binding site to the active site going through the interface residues of Domain I and II; and this path was either weakened or lost in the presence of some of the mutations. Overall, the results of this study revealed crucial aspects that need to be considered in drug discovery in COVID-19 specifically and in general for rational computational drug design purposes.

Crystal structure of oleate hydratase from Stenotrophomonas sp. KCTC 12332 reveals conformational plasticity surrounding the FAD binding site

2018 ◽  
Vol 499 (4) ◽  
pp. 772-776 ◽  
Author(s):  
Ae Kyung Park ◽  
Gyeong Hweon Lee ◽  
Do Wan Kim ◽  
Eun Hyuk Jang ◽  
Ha Taek Kwon ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Conformational Plasticity ◽  
Fad Binding ◽  
Oleate Hydratase

The stability of mRNA from the gsiB gene of Bacillus subtilis is dependent on the presence of a strong ribosome binding site

1998 ◽  
Vol 258 (5) ◽  
pp. 538-545 ◽  
Author(s):  
B. Jürgen ◽  
T. Schweder ◽  
M. Hecker
Keyword(s):  
Bacillus Subtilis ◽  
Binding Site ◽  
Ribosome Binding Site ◽  
Ribosome Binding ◽  
The Stability

Mutagenesis Study of the 2Fe-2S Center and the FAD Binding Site of the Na+-Translocating NADH:Ubiquinone Oxidoreductase fromVibrio cholerae†

Biochemistry ◽  
2004 ◽  
Vol 43 (38) ◽  
pp. 12322-12330 ◽  
Author(s):  
Blanca Barquera ◽  
Mark J. Nilges ◽  
Joel E. Morgan ◽  
Leticia Ramirez-Silva ◽  
Weidong Zhou ◽  
...  
Keyword(s):  
Binding Site ◽  
Nadh:Ubiquinone Oxidoreductase ◽  
Mutagenesis Study ◽  
Fad Binding

scholarly journals Multiple Mechanisms Are Used for Growth Rate and Stringent Control of leuV Transcriptional Initiation inEscherichia coli

1999 ◽  
Vol 181 (18) ◽  
pp. 5771-5782 ◽  
Author(s):  
Dmitry K. Pokholok ◽  
Maria Redlak ◽  
Charles L. Turnbough ◽  
Sara Dylla ◽  
Walter M. Holmes
Keyword(s):  
Growth Rate ◽  
Binding Site ◽  
Transcription Initiation ◽  
Core Promoter ◽  
Cellular Level ◽  
Structural Variants ◽  
Stringent Control ◽  
The Stability

ABSTRACT Expression of the Escherichia coli leuV operon, which contains three tRNA1 Leu genes, is regulated by several mechanisms including growth-rate-dependent control (GRDC) and stringent control (SC). Structural variants of the leuV promoter which differentially affect these regulatory responses have been identified, suggesting that promoter targets for GRDC and SC may be different and that GRDC of the leuV promoter occurs in the absence of guanosine 3′,5′-bisdiphosphate. To determine the mechanisms of the leuV promoter regulation, we have examined the stability of promoter open complexes and the effects of nucleotide triphosphate (NTP) concentration on the efficiency of theleuV promoter and its structural variants in vitro and in vivo. The leuV promoter open complexes were an order of magnitude more stable to heparin challenge than those ofrrnBp 1. The major initiating nucleotide GTP as well as other NTPs increased the stability of the leuVpromoter open complexes. When the cellular level of purine triphosphates was increased at slower growth rates by pyrimidine limitation, a 10% reduction in leuV promoter activity was seen. It therefore appears that transcription initiation from theleuV promoter is less sensitive to changes in intracellular NTP concentration than that from rrnBp 1. Comparative analysis of regulation of the leuV promoter with and without upstream activating sequences (UAS) demonstrated that the binding site for factor of inversion stimulation (FIS) located in UAS is essential for maximal GRDC. Moreover, the presence of UAS overcame the effects of leuV promoter mutations, which abolished GRDC of the leuV core promoter. However, although the presence of putative FIS binding site was essential for optimal GRDC, both mutant and wild-type leuV promoters containing UAS showed improved GRDC in a fis mutant background, suggesting that FIS protein is an important but not unique participant in the regulation of the leuV promoter.

scholarly journals A Novel method for Thermodynamic Study on the Binding of Milk Carrier protein of BLG-A with Cr+3

2009 ◽  
Vol 11 (4) ◽  
pp. 24-29
Author(s):  
G. Behbehania ◽  
A. Divsalar ◽  
A. Saboury
Keyword(s):  
Binding Site ◽  
Equilibrium Constants ◽  
Thermodynamic Study ◽  
Titration Calorimetry ◽  
Carrier Protein ◽  
Novel Method ◽  
The Stability ◽  
New Equation ◽  
Β Lactoglobulin ◽  
Association Equilibrium

A Novel method for Thermodynamic Study on the Binding of Milk Carrier protein of BLG-A with Cr+3 Thermodynamics of the interaction between Cr3+ with β-lactoglobulin type A (BLG-A) was investigated at pH 7.0 and 37°C by isothermal titration calorimetry. A new method to follow the effect of Cr3+ on the stability of BLG-A was introduced. The new solvation model was used to reproduce the enthalpies of BLG-A+ Cr3+ interactions over the whole range of Cr3+ concentrations. The solvation parameters recovered from the new equation are attributed to the structural change of BLG-A and its biological activity. The results obtained indicate that there is a set of two identical binding sites for Cr3+ ions with positive cooperativity. The association equilibrium constants are 14.39 and 0.49 mM-1 for the first and second binding site, respectively. The enthalpy of binding for one mole of Cr+3 ion to one mole of the binding site on BLG-A (ΔH=104.60 kJ mol-1) is obtained.

scholarly journals Structural prerequisites for CRM1-dependent nuclear export signaling peptides: accessibility, adapting conformation, and the stability at the binding site

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoonji Lee ◽  
Jimin Pei ◽  
Jordan M. Baumhardt ◽  
Yuh Min Chook ◽  
Nick V. Grishin
Keyword(s):  
Binding Site ◽  
Nuclear Export ◽  
Signaling Peptides ◽  
The Stability

FAD-binding site of glutathione reductase

1982 ◽  
Vol 160 (2) ◽  
pp. 287-308 ◽  
Author(s):  
G.E. Schulz ◽  
R.H. Schirmer ◽  
E.F. Pai
Keyword(s):  
Glutathione Reductase ◽  
Binding Site ◽  
Fad Binding

scholarly journals Mechanism of RNA stabilization and translational activation by a pentatricopeptide repeat protein

2010 ◽  
Vol 108 (1) ◽  
pp. 415-420 ◽  
Author(s):  
Jana Prikryl ◽  
Margarita Rojas ◽  
Gadi Schuster ◽  
Alice Barkan
Keyword(s):  
Binding Site ◽  
Large Family ◽  
Pentatricopeptide Repeat ◽  
Repeat Proteins ◽  
Rna Remodeling ◽  
Ppr Proteins ◽  
Maize Protein ◽  
Rna Stabilization ◽  
The Stability

Pentatricopeptide repeat (PPR) proteins comprise a large family of helical repeat proteins that bind RNA and modulate organellar RNA metabolism. The mechanisms underlying the functions attributed to PPR proteins are unknown. We describe in vitro studies of the maize protein PPR10 that clarify how PPR10 modulates the stability and translation of specific chloroplast mRNAs. We show that recombinant PPR10 bound to its native binding site in the chloroplast atpI–atpH intergenic region (i) blocks both 5′→3′ and 3′→ 5 exoribonucleases in vitro; (ii) is sufficient to define the native processed atpH mRNA 5′-terminus in conjunction with a generic 5′→3′ exoribonuclease; and (iii) remodels the structure of the atpH ribosome-binding site in a manner that can account for PPR10’s ability to enhance atpH translation. In addition, we show that the minimal PPR10-binding site spans 17 nt. We propose that the site-specific barrier and RNA remodeling activities of PPR10 are a consequence of its unusually long, high-affinity interface with single-stranded RNA, that this interface provides a functional mimic to bacterial small RNAs, and that analogous activities underlie many of the biological functions that have been attributed to PPR proteins.

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