Identification of a peptide ligand for human ALDH3A1 through peptide phage display: Prediction and characterization of protein interaction sites and inhibition of ALDH3A1 enzymatic activity

Voulgaridou, Georgia-Persephoni; Theologidis, Vasileios; Xanthis, Vasileios; Papagiannaki, Eleni; Tsochantaridis, Ilias; Fadouloglou, Vasiliki E.; Pappa, Aglaia

doi:10.3389/fmolb.2023.1161111

Cited by 6 publications

(4 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In HO, the most coupled genes are Aldh3a1 and Gapdh , with only 10 (25.5%) synergistic partners, while the uncoupled genes (no partners) are Acss2 , Acyp2 , Eno4 , Gapdhs , and Pfkl. Aldh3a1 is a putative biomarker of lung cancer [ 70 ], while Gapdh was reported as critical for stem cell therapy of pulmonary hypertensive females [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Deregulation in Pulmonary Hypertension

Mathew

Iacobaş

Huang

et al. 2023

CIMB

View full text Add to dashboard Cite

The high morbidity and mortality rate of pulmonary arterial hypertension (PAH) is partially explained by metabolic deregulation. The present study complements our previous publication in “Genes” by identifying significant increases of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid-derived 2-like 2 (Nfe2l2) in three standard PAH rat models. PAH was induced by subjecting the animals to hypoxia (HO), or by injecting with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with novel analyses of previously published transcriptomic datasets of the animal lungs from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis, and fructose and mannose pathways. According to the transcriptomic distance, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes, and replaced phosphomannomutase 2 (Pmm2) with phosphomannomutase 1 (Pmm1) in the center of the fructose and mannose metabolism. We also found significant regulation of key genes involved in PAH channelopathies. In conclusion, our data show that metabolic dysregulation is a major PAH pathogenic factor.

show abstract

Section: Discussionmentioning

confidence: 99%

Metabolic Deregulation in Pulmonary Hypertension

Mathew

Iacobaş

Huang

et al. 2023

CIMB

View full text Add to dashboard Cite

show abstract

“…In HO, the most coupled genes are: Aldh3a1 and Gapdh with only 10 (25.5%) synergistic partners, while the uncoupled genes (no partners) are: Acss2, Acyp2, Eno4, Gapdhs, Pfkl. Aldh3a1 is a putative biomarker of lung cancer [57], while Gapdh was reported as critical for stem cell therapy of pulmonary hypertensive females [58].…”

Section: Discussionmentioning

confidence: 99%

Metabolic Deregulation in Pulmonary Hypertension

Mathew¹,

Iacobaş²,

Huang³

et al. 2023

Preprint

View full text Add to dashboard Cite

The high morbidity and mortality rate of the pulmonary arterial hypertension (PAH) is partially explained by the metabolic deregulation associated with the disease. The present study identified statistically significant increase of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid derived 2, like 2 (Nfe2l2) on three standard PAH rat models and their healthy counterpart. PAH was induced by subjecting the animals to hypoxia (HO group) or by injecting them with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with the gene expression profiling of the animal lungs analyzed from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the genomic fabrics of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis and fructose and manose pathways. According to the novel transcriptomic distance criterion, the most comprehensive measure of the transcriptomic alteration, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes and replaced Pmm2 with Pmm1 in the center of the fructose and mannose metabolism. Our data show that metabolic dysregulation is a major pathogenic factor of the PAH.

show abstract

“…Enzymatic studies showed that the peptide exhibits a significant inhibitory effect against ALDH3A1's activity which is comparable to CB29 inhibition. Furthermore, bioinformatic analysis identified an area close to the substrate binding site as the most probable peptide binding site on the protein [249].…”

Section: Aldh2 Specific Inhibitorsmentioning

confidence: 99%

Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer

Xanthis,

Mantso,

Dimtsi

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

The superfamily of human aldehyde dehydrogenases (hALDHs) consists of 19 isoenzymes which are critical for several physiological and biosynthetic processes and play a major role in the organism’s detoxification via the NAD(P) dependent oxidation of numerous endogenous and exogenous aldehyde substrates to their corresponding carboxylic acids. Over the last decades, ALDHs have been the subject of several studies as it was revealed that their differential expression patterns in various cancer types are associated either with carcinogenesis or promotion of cell survival. Here, we attempt to provide a thorough review of hALDHs’ diverse functions and 3D structures with particular emphasis on their role in cancer pathology and resistance to chemotherapy. We are especially interested in findings regarding the association of structural features and their changes with effects on enzymes’ functionalities. Moreover, we provide an updated outline of the hALDHs inhibitors utilized in experimental or clinical settings for cancer therapy. Overall, this review aims to provide a better understanding of the impact of ALDHs in cancer pathology and therapy from a structural perspective.

show abstract

Identification of a peptide ligand for human ALDH3A1 through peptide phage display: Prediction and characterization of protein interaction sites and inhibition of ALDH3A1 enzymatic activity

Cited by 6 publications

References 55 publications

Metabolic Deregulation in Pulmonary Hypertension

Metabolic Deregulation in Pulmonary Hypertension

Metabolic Deregulation in Pulmonary Hypertension

Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer

Contact Info

Product

Resources

About