scholarly journals Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hyung-Seop Youn ◽  
Tae Gyun Kim ◽  
Mun-Kyoung Kim ◽  
Gil Bu Kang ◽  
Jung Youn Kang ◽  
...  
Keyword(s):  
Catalytic Mechanism ◽  
De Novo ◽  
Nad Biosynthesis ◽  
Key Enzyme ◽  
Structural Insights ◽  
Quinolinate Phosphoribosyltransferase

Structural insights into the catalytic mechanism of the yeast pyridoxal 5-phosphate synthase Snz1

2010 ◽  
Vol 432 (3) ◽  
pp. 445-454 ◽  
Author(s):  
Xuan Zhang ◽  
Yan-Bin Teng ◽  
Jian-Ping Liu ◽  
Yong-Xing He ◽  
Kang Zhou ◽  
...  
Keyword(s):  
Binding Site ◽  
Vitamin B6 ◽  
Active Sites ◽  
Biochemical Analysis ◽  
Catalytic Mechanism ◽  
De Novo ◽  
Active Form ◽  
Dihydroxyacetone Phosphate ◽  
Final Destination ◽  
Structural Insights

In most eubacteria, fungi, apicomplexa, plants and some metazoans, the active form of vitamin B6, PLP (pyridoxal 5-phosphate), is de novo synthesized from three substrates, R5P (ribose 5-phosphate), DHAP (dihydroxyacetone phosphate) and ammonia hydrolysed from glutamine by a complexed glutaminase. Of the three active sites of DXP (deoxyxylulose 5-phosphate)independent PLP synthase (Pdx1), the R5P isomerization site has been assigned, but the sites for DHAP isomerization and PLP formation remain unknown. In the present study, we present the crystal structures of yeast Pdx1/Snz1, in apo-, G3P (glyceraldehyde 3-phosphate)- and PLP-bound forms, at 2.3, 1.8 and 2.2 Å (1 Å=0.1 nm) respectively. Structural and biochemical analysis enabled us to assign the PLP-formation site, a G3P-binding site and a G3P-transfer site. We propose a putative catalytic mechanism for Pdx1/Snz1 in which R5P and DHAP are isomerized at two distinct sites and transferred along well-defined routes to a final destination for PLP synthesis.

scholarly journals Knockdown of Quinolinate Phosphoribosyltransferase Results in Decreased Salicylic Acid-Mediated Pathogen Resistance in Arabidopsis thaliana

2021 ◽  
Vol 22 (16) ◽  
pp. 8484
Author(s):  
Shengchun Li ◽  
Haiyan Ding ◽  
Yi Deng ◽  
Jiang Zhang
Keyword(s):  
Arabidopsis Thaliana ◽  
Salicylic Acid ◽  
Pseudomonas Syringae ◽  
De Novo ◽  
Oxidative Stress Marker ◽  
Marker Genes ◽  
Avirulent Strain ◽  
Wild Type ◽  
Nad Biosynthesis ◽  
Quinolinate Phosphoribosyltransferase

Nicotinamide adenine dinucleotide (NAD) is a pivotal coenzyme that has emerged as a central hub linking redox equilibrium and signal transduction in living cells. The homeostasis of NAD is required for plant growth, development, and adaption to environmental stresses. Quinolinate phosphoribosyltransferase (QPRT) is a key enzyme in NAD de novo synthesis pathway. T-DNA-based disruption of QPRT gene is embryo lethal in Arabidopsis thaliana. Therefore, to investigate the function of QPRT in Arabidopsis, we generated transgenic plants with decreased QPRT using the RNA interference approach. While interference of QPRT gene led to an impairment of NAD biosynthesis, the QPRT RNAi plants did not display distinguishable phenotypes under the optimal condition in comparison with wild-type plants. Intriguingly, they exhibited enhanced sensitivity to an avirulent strain of Pseudomonas syringae pv. tomato (Pst-avrRpt2), which was accompanied by a reduction in salicylic acid (SA) accumulation and down-regulation of pathogenesis-related genes expression as compared with the wild type. Moreover, oxidative stress marker genes including GSTU24, OXI1, AOX1 and FER1 were markedly repressed in the QPRT RNAi plants. Taken together, these data emphasized the importance of QPRT in NAD biosynthesis and immunity defense, suggesting that decreased antibacterial immunity through the alteration of NAD status could be attributed to SA- and reactive oxygen species-dependent pathways.

Structural insights into the catalytic mechanism of sphingomyelinases D and evolutionary relationship to glycerophosphodiester phosphodiesterases

2006 ◽  
Vol 342 (1) ◽  
pp. 323-329 ◽  
Author(s):  
Mário T. Murakami ◽  
Matheus Freitas Fernandes-Pedrosa ◽  
Sonia A. de Andrade ◽  
Azat Gabdoulkhakov ◽  
Christian Betzel ◽  
...  
Keyword(s):  
Catalytic Mechanism ◽  
Evolutionary Relationship ◽  
Structural Insights

Structural insights into the specificity and catalytic mechanism of mycobacterial nucleotide pool sanitizing enzyme MutT2

2018 ◽  
Vol 204 (3) ◽  
pp. 449-456 ◽  
Author(s):  
Amandeep Singh ◽  
Sheikh Mohammad Arif ◽  
Pau Biak Sang ◽  
Umesh Varshney ◽  
M. Vijayan
Keyword(s):  
Catalytic Mechanism ◽  
Structural Insights

scholarly journals Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Marcus O. W. Grimm ◽  
Sven Grösgen ◽  
Tatjana L. Rothhaar ◽  
Verena K. Burg ◽  
Benjamin Hundsdörfer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
De Novo ◽  
Physiological Function ◽  
Proteolytic Processing ◽  
Sphingolipid Metabolism ◽  
Amyloid Beta Peptides ◽  
Beta Peptides ◽  
Coa Transferase ◽  
Key Enzyme

Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipidde novosynthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic ADpostmortembrains, suggesting that SPT is involved in AD pathology.

scholarly journals Chemical Stability of Ascorbic Acid Integrated into Commercial Products: A Review on Bioactivity and Delivery Technology

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 153
Author(s):  
Xin Yin ◽  
Kaiwen Chen ◽  
Hao Cheng ◽  
Xing Chen ◽  
Shuai Feng ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Active Site ◽  
De Novo ◽  
Food Matrix ◽  
De Novo Synthesis ◽  
Nutritional Characteristics ◽  
Gulonolactone Oxidase ◽  
Key Enzyme ◽  
Commercial Applications ◽  
Delivery Technology

The L-enantiomer of ascorbic acid is commonly known as vitamin C. It is an indispensable nutrient and plays a key role in retaining the physiological process of humans and animals. L-gulonolactone oxidase, the key enzyme for the de novo synthesis of ascorbic acid, is lacking in some mammals including humans. The functionality of ascorbic acid has prompted the development of foods fortified with this vitamin. As a natural antioxidant, it is expected to protect the sensory and nutritional characteristics of the food. It is thus important to know the degradation of ascorbic acid in the food matrix and its interaction with coexisting components. The biggest challenge in the utilization of ascorbic acid is maintaining its stability and improving its delivery to the active site. The review also includes the current strategies for stabilizing ascorbic acid and the commercial applications of ascorbic acid.

Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis

2011 ◽  
Vol 436 (3) ◽  
pp. 729-739 ◽  
Author(s):  
Marcio V. B. Dias ◽  
William C. Snee ◽  
Karen M. Bromfield ◽  
Richard J. Payne ◽  
Satheesh K. Palaninathan ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Targets ◽  
Structural Investigation ◽  
Catalytic Mechanism ◽  
Shikimate Pathway ◽  
Structural Rearrangement ◽  
Competitive Inhibitors ◽  
Structural Insights ◽  
Potential Drug Targets

The shikimate pathway is essential in Mycobacterium tuberculosis and its absence from humans makes the enzymes of this pathway potential drug targets. In the present paper, we provide structural insights into ligand and inhibitor binding to 3-dehydroquinate dehydratase (dehydroquinase) from M. tuberculosis (MtDHQase), the third enzyme of the shikimate pathway. The enzyme has been crystallized in complex with its reaction product, 3-dehydroshikimate, and with six different competitive inhibitors. The inhibitor 2,3-anhydroquinate mimics the flattened enol/enolate reaction intermediate and serves as an anchor molecule for four of the inhibitors investigated. MtDHQase also forms a complex with citrazinic acid, a planar analogue of the reaction product. The structure of MtDHQase in complex with a 2,3-anhydroquinate moiety attached to a biaryl group shows that this group extends to an active-site subpocket inducing significant structural rearrangement. The flexible extensions of inhibitors designed to form π-stacking interactions with the catalytic Tyr24 have been investigated. The high-resolution crystal structures of the MtDHQase complexes provide structural evidence for the role of the loop residues 19–24 in MtDHQase ligand binding and catalytic mechanism and provide a rationale for the design and efficacy of inhibitors.

scholarly journals Suppression of Induced Resistance in Cucumber Through Disruption of the Flavonoid Pathway

2005 ◽  
Vol 95 (1) ◽  
pp. 114-123 ◽  
Author(s):  
Bourlaye Fofana ◽  
Nicole Benhamou ◽  
David J. McNally ◽  
Caroline Labbé ◽  
Armand Séguin ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Induced Resistance ◽  
De Novo ◽  
Ultrastructural Changes ◽  
Protein Accumulation ◽  
Complete Suppression ◽  
Flavonoid Pathway ◽  
Induced Disease Resistance ◽  
Key Enzyme ◽  
Biochemical Analyses

In this study, cucumber plants (Cucumis sativus) expressing induced resistance against powdery mildew (caused by Podosphaera xanthii) were infiltrated with inhibitors of cinnamate 4-hydroxylase, 4-coumarate:CoA ligase (4CL), and chalcone synthase (CHS) to evaluate the role of flavonoid phytoalexin production in induced disease resistance. Light and transmission electron microscopy demonstrated ultrastructural changes in inhibited plants, and biochemical analyses determined levels of CHS and β-glucosidase enzyme activity and 4CL protein accumulation. Our results showed that elicited plants displayed a high level of induced resistance. In contrast, down regulation of CHS, a key enzyme of the flavonoid pathway, resulted in nearly complete suppression of induced resistance, and microscopy confirmed the development of healthy fungal haustoria within these plants. Inhibition of 4CL ligase, an enzyme largely responsible for channeling phenylpropanoid metabolites into the lignin pathway, had little effect on induced disease resistance. Biochemical analyses revealed similar levels of 4CL protein accumulation for all treatments, suggesting no alterations of nontargeted functions within inhibited plants. Collectively, the results of this study support the idea that induced resistance in cucumber is largely correlated with rapid de novo biosynthesis of flavonoid phytoalexin compounds.

α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis

2018 ◽  
Vol 61 (3) ◽  
pp. 745-759 ◽  
Author(s):  
Roberto Pellicciari ◽  
Paride Liscio ◽  
Nicola Giacchè ◽  
Francesca De Franco ◽  
Andrea Carotti ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
De Novo ◽  
Nicotinamide Adenine ◽  
Nad Biosynthesis
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