scholarly journals Phosphate Binding in the Active Site of Alkaline Phosphatase and the Interactions of 2-Nitrosoacetophenone with Alkaline Phosphatase-Induced Small Structural Changes

2004 ◽  
Vol 86 (6) ◽  
pp. 3873-3881 ◽  
Author(s):  
Le Zhang ◽  
René Buchet ◽  
Gérard Azzar
Keyword(s):  
Alkaline Phosphatase ◽  
Active Site ◽  
Structural Changes ◽  
Phosphate Binding

scholarly journals Phosphate Binding to Alkaline Phosphatase

1970 ◽  
Vol 245 (19) ◽  
pp. 4968-4975 ◽  
Author(s):  
Meredithe L. Applebury ◽  
Barbara P. Johnson ◽  
Joseph E. Coleman
Keyword(s):  
Alkaline Phosphatase ◽  
Phosphate Binding

scholarly journals A summary of feed additives, intestinal health and intestinal alkaline phosphatase in piglet nutrition

2020 ◽  
Vol 65 (No. 8) ◽  
pp. 281-294
Author(s):  
Jansller Genova ◽  
Antonio Melo ◽  
Paulo Rupolo ◽  
Silvana Carvalho ◽  
Leandro Costa ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Structural Changes ◽  
Stress Factors ◽  
Intestinal Microbiome ◽  
Resistant Bacteria ◽  
Feeding Strategies ◽  
High Morbidity ◽  
Intestinal Health ◽  
Growth Promoters ◽  
Intestinal Alkaline Phosphatase

Weaning is considered the “critical window” in the piglet’s life because it is associated with several stress factors, such as loss of contact with the mother and original litter, solid diet, environmental and structural changes, and the establishment of a new hierarchy. During this abrupt period, several events such as reduced feed intake, high morbidity, susceptibility to enteric infections and post-weaning diarrhoea are observed. The nutritional landscape of the piglet gut is modified, which can compromise the maturity of the gastrointestinal system, the stable intestinal microbiome and the active immunity developed as an indicator of intestinal health. However, with increased awareness of feed safety issues and the development of drug-resistant bacteria, the interest in producing pigs without the use of antimicrobial growth promoters (AGP) is increasing, since long-term use and therapeutic doses of AGP can contribute to the reduction of bacterial diversity and increase of inflammatory bowel disease (IBD). Thus, the most widely researched alternatives include the use of feed additives, feeding strategies, nutraceuticals/functional foods and available handling that can reduce the risk of IBD beyond basic nutritional functions. Studies have reported intestinal alkaline phosphatase as a new nutritional therapy associated with intestinal health which may be a “key additive” in the AGP replacement. In this review article, the purpose is to show some current aspects of feed additive research, addressing a concept of the “intestinal health” from different points of view and properties of alkaline phosphatase.

scholarly journals Evidence for the importance of arginine residues in pig kidney alkaline phosphatase

1979 ◽  
Vol 181 (1) ◽  
pp. 137-142 ◽  
Author(s):  
M N Woodroofe ◽  
P J Butterworth
Keyword(s):  
Alkaline Phosphatase ◽  
Active Site ◽  
Competitive Inhibitor ◽  
Arginine Residue ◽  
Pig Kidney ◽  
Close Proximity ◽  
Arginine Residues ◽  
Km Value ◽  
Uncompetitive Inhibitor ◽  
Kidney Alkaline Phosphatase

The arginine-specific reagents 2,3-butanedione and phenylglyoxal inactivate pig kidney alkaline phosphatase. As inactivation proceeds there is a progressive fall in Vmax. of the enzyme, but no demonstrable change in the Km value for substrate. Pi, a competitive inhibitor, and AMP, a substrate of the enzyme, protect alkaline phosphatase against the arginine-specific reagents. These effects are explicable by the assumption that the enzyme contains an essential arginine residue at the active site. Protection is also afforded by the uncompetitive inhibitor NADH through a partially competive action against the reagents. Enzyme that has been exposed to the reagents has a decreased sensitivity to NADH inhibition. It is suggested that an arginine residue is important for NADH binding also, although this residue is distinct from that at the catalytic site. The protection given by NADH against loss of activity is indicative of the close proximity of the active and NADH sites.

scholarly journals The Loop of the TPR1 Subdomain of Phi29 DNA Polymerase Plays a Pivotal Role in Primer-Terminus Stabilization at the Polymerization Active Site

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 648
Author(s):  
del Prado ◽  
Santos ◽  
Lázaro ◽  
Salas ◽  
de Vega
Keyword(s):  
Dna Polymerase ◽  
Active Site ◽  
Structural Changes ◽  
Binding Capacity ◽  
Dna Polymerases ◽  
Crystallographic Structure ◽  
Genome Replication ◽  
Terminal Protein ◽  
Phi29 Dna Polymerase

Bacteriophage Phi29 DNA polymerase belongs to the protein-primed subgroup of family B DNA polymerases that use a terminal protein (TP) as a primer to initiate genome replication. The resolution of the crystallographic structure showed that it consists of an N-terminal domain with the exonuclease activity and a C-terminal polymerization domain. It also has two subdomains specific of the protein-primed DNA polymerases; the TP Regions 1 (TPR1) that interacts with TP and DNA, and 2 (TPR2), that couples both processivity and strand displacement to the enzyme. The superimposition of the structures of the apo polymerase and the polymerase in the polymerase/TP heterodimer shows that the structural changes are restricted almost to the TPR1 loop (residues 304–314). In order to study the role of this loop in binding the DNA and the TP, we changed the residues Arg306, Arg308, Phe309, Tyr310, and Lys311 into alanine, and also made the deletion mutant Δ6 lacking residues Arg306–Lys311. The results show a defective TP binding capacity in mutants R306A, F309A, Y310A, and Δ6. The additional impaired primer-terminus stabilization at the polymerization active site in mutants Y310A and Δ6 allows us to propose a role for the Phi29 DNA polymerase TPR1 loop in the proper positioning of the DNA and TP-priming 3’-OH termini at the preinsertion site of the polymerase to enable efficient initiation and further elongation steps during Phi29 TP-DNA replication.

scholarly journals Cheminformatics Modeling of Closantel Analogues for Treating River Blindness

2020 ◽  
Author(s):  
Melaine A. Kuenemann ◽  
Phyo Phyo Zin ◽  
Sravya Kuchibhotla ◽  
Denis Fourches
Keyword(s):  
Active Site ◽  
Structural Changes ◽  
Parasitic Nematode ◽  
Chemical Space ◽  
Therapeutic Agents ◽  
Binding Modes ◽  
River Blindness ◽  
Structure Activity ◽  
Potential Binding ◽  
Biological Target

<p></p><p>Onchocerciasis (also known as river blindness<i>)</i> is a neglected tropical disease caused by the <i>Onchocerca volvulus</i> parasitic nematode. Currently, the only approved drug for treating this disease is ivermectin, which is a broad-spectrum antiparasitic agent. However, signs of resistance towards ivermectin have started to emerge. New therapeutic agents are thus urgently needed. The OvCHT1 chitinase enzyme from <i>O. volvulus</i> has been established as a relevant biological target for combatting river blindness. The veterinary anthelmintic drug closantel has been found to be a potent, micro-molar OvCHT1 inhibitor. Herein, we investigated the chemical space of closantel and all its synthesized analogues, focusing on the analysis of their potential binding modes towards OvCHT1. First, we conducted an unsupervised hierarchical clustering to group highly similar analogues and explore structure-activity relationships. Second, we conducted a structure-based molecular docking to predict and study the binding modes of all 57 closantel analogues in the active site of OvCHT1. Third, we screened more than 4 million lead-like compounds from the ZINC library to identify other structurally similar ligands that could potentially bind to OvCHT1. The cheminformatics analysis of the closantel analogues illustrated how minor structural changes in closantel analogues can impact their OvCHT1 activity.</p><p></p>

P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency

2020 ◽  
Vol 168 (5) ◽  
pp. 557-567
Author(s):  
Wanitcha Rachadech ◽  
Yusuke Kato ◽  
Rabab M Abou El-Magd ◽  
Yuji Shishido ◽  
Soo Hyeon Kim ◽  
...  
Keyword(s):  
Amino Acid ◽  
Conformational Changes ◽  
Active Site ◽  
Structural Changes ◽  
Catalytic Efficiency ◽  
Acid Oxidase ◽  
Wild Type ◽  
Amino Acid Oxidase ◽  
Adenine Ring ◽  
The Impact

Abstract Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7–0.9 µM) compared with wild-type (1.2–2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure–function relationship of human DAO.

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