Amino Acids最新文献

{"title":"Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls","authors":"Adrian Post,&nbsp;Dion Groothof,&nbsp;Daan Kremer,&nbsp;Tim J. Knobbe,&nbsp;Willem Abma,&nbsp;Christa A. Koops,&nbsp;Dimitrios Tsikas,&nbsp;Theo Wallimann,&nbsp;Robin P.F. Dullaart,&nbsp;Casper F.M. Franssen,&nbsp;Ido P. Kema,&nbsp;M. Rebecca Heiner-Fokkema,&nbsp;Stephan J.L. Bakker","doi":"10.1007/s00726-024-03401-w","DOIUrl":"10.1007/s00726-024-03401-w","url":null,"abstract":"<div><p>Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all <i>P</i> &gt; 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, <i>P</i> &lt; 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, <i>P</i> &lt; 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both <i>P</i> &lt; 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both <i>P</i> &lt; 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; <i>P</i> = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; <i>P</i> &lt; 0.001). These associations were fully mediated (93% and 95%; <i>P</i> &lt; 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.</p><p>Trial registration ID: NCT02811835.</p><p><b>Trial registration URL</b>: https://clinicaltrials.gov/ct2/show/NCT02811835.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined assessment of lysine and N-acetyl cadaverine levels assist as a potential biomarker of the smoker periodontitis","authors":"Md Haroon Rashid,&nbsp;Sandhya Pavan Kumar Yellarthi,&nbsp;Pavan Kumar Yellarthi,&nbsp;Brinda Goda Lakshmi Didugu,&nbsp;Anitha Mamillapalli","doi":"10.1007/s00726-024-03396-4","DOIUrl":"10.1007/s00726-024-03396-4","url":null,"abstract":"<div><p>Periodontitis is an inflammatory condition of supporting structures of teeth leading to attachment and bone loss. Cigarette smoking is the single most important and modifiable risk factor with 5 to 20-fold susceptibility for periodontal diseases. Reverse smoking is a peculiar habit of smoking where the lit end is kept inside the mouth, which is predominant in the northern coastal districts of Andhra Pradesh. Polyamines are biologically active amines involved in tissue regeneration and modulation of inflammation. The study aimed to evaluate polyamines and check their utility as a marker in detection of periodontitis among different groups. Total polyamine levels showed significant increase in reverse smokers with periodontitis when compared to the other groups. Qualitative analysis by thin layer chromatography showed three polyamine bands with varying intensity among the different groups. Mass spectrometric and NMR analyses of the three bands identified them as N1, N8-diacetyl spermidine, <i>N</i>-acetyl cadaverine and lysine. Most significantly elevated levels of lysine was observed in the smoker and reverse smoker periodontitis groups when compared to healthy and non-smoker periodontitis groups. The significantly elevated levels of <i>N</i>-acetyl cadaverine could be responsible for the more destruction of periodontium in the reverse smoker group. Antioxidant potential decreased significantly in different smoker periodontitis groups. The present study suggests that the quantitative analysis of salivary polyamines, lysine and <i>N</i>-acetyl cadaverine can aid as an easy noninvasive diagnostic method for assessing the periodontal status, especially in smokers.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel ACE inhibitory peptide from Pelodiscus sinensis Wiegmann meat water-soluble protein hydrolysate","authors":"Pengying Liao,&nbsp;Huayu Liu,&nbsp;Xueqin Sun,&nbsp;Xinrui Zhang,&nbsp;Miao Zhang,&nbsp;Xianyou Wang,&nbsp;Jun Chen","doi":"10.1007/s00726-024-03399-1","DOIUrl":"10.1007/s00726-024-03399-1","url":null,"abstract":"<div><p><i>Pelodiscus sinensis</i> meat is a nutritional food and tonic with angiotensin-converting enzyme (ACE) inhibitory activities. To identify the bioactive substances responsible, several bioinformatics methods were integrated to enable a virtual screening for bioactive peptides in proteins identified within a water-soluble protein fraction of <i>Pelodiscus sinensis</i> meat by Shotgun proteomics. The peptides were generated from the identified proteins by in silico proteolysis using six proteases. A comparison of the numbers of proteins suitable for digestion with each enzyme and the iBAQ (intensity-based absolute quantification) values for these proteins revealed that bromelain and papain were the most suitable proteases for this sample. Next, the water solubility, toxicity, and ADMET (absorption/distribution/metabolism/excretion/toxicity) properties of these peptides were evaluated in silico. Finally, a novel ACE inhibitory peptide IEWEF with an IC₅₀ value of 41.33 µM was identified. The activity of the synthesized peptide was verified in vitro, and it was shown to be a non-competitive ACE inhibitor. Molecular docking revealed that IEWEF could tightly bind to C-ACE, and N-ACE with energies less than 0 kJ mol⁻¹, and the peptide IEWEF can form hydrogen bonds with C-ACE and N-ACE respectively. These results provide evidence that bioactive peptides in the water-soluble protein fraction account for (at least) some of the ACE inhibitory activities observed in <i>Pelodiscus sinensis</i> meat. Furthermore, our research provides a workflow for the efficient identification of novel ACE inhibitory peptides from complex protein mixtures.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03399-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute effects of oral mesna administration on the full amino acid profile and 3-methylhistidine: secondary results from the CYLOB dose-finding study","authors":"Thomas Olsen,&nbsp;Amany Elshorbagy,&nbsp;Emma Stolt,&nbsp;Anders Åsberg,&nbsp;Hasse K. Zaré,&nbsp;Nasser E. Bastani,&nbsp;Helga Refsum,&nbsp;Kjetil Retterstøl,&nbsp;Kathrine J. Vinknes","doi":"10.1007/s00726-024-03398-2","DOIUrl":"10.1007/s00726-024-03398-2","url":null,"abstract":"<div><p>Plasma total cysteine (tCys) is strongly associated with fat mass in humans. Mesna lowers plasma tCys in a dose-dependent manner, but it is not known whether it interferes with metabolism of other amino acids or protein. In this Phase-1 study, we show that a single dose of mesna administered at 400, 800, 1200 or 1600 mg to 6–7 individuals per dose only slightly affects amino acid profiles, with increases in plasma valine across dose levels. There were no effects of mesna on 3-methylhistidine, a marker of protein breakdown.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma d-asparagine and the d/l-serine ratio reflect chronic kidney diseases in children regardless of physique","authors":"Toshimasa Morishita,&nbsp;Naoto Nishizaki,&nbsp;Sakiko Taniguchi,&nbsp;Shinsuke Sakai,&nbsp;Tomonori Kimura,&nbsp;Masashi Mita,&nbsp;Mayu Nakagawa,&nbsp;Amane Endo,&nbsp;Yoshiyuki Ohtomo,&nbsp;Masato Yasui,&nbsp;Toshiaki Shimizu,&nbsp;Jumpei Sasabe","doi":"10.1007/s00726-024-03400-x","DOIUrl":"10.1007/s00726-024-03400-x","url":null,"abstract":"<div><p>Biomarkers that accurately reflect renal function are essential in management of chronic kidney diseases (CKD). However, in children, age/physique and medication often alter established renal biomarkers. We studied whether amino acid enantiomers in body fluids correlate with renal function and whether they are influenced by physique or steroid medication during development. We conducted a prospective study of children 2 to 18 years old with and without CKD. We analyzed associations of serine/asparagine enantiomers in body fluids with major biochemical parameters as well as physique. To study consequences of kidney dysfunction and steroids on serine/asparagine enantiomers, we generated juvenile mice with uninephrectomy, ischemic reperfusion injury, or dexamethasone treatment. We obtained samples from 27 children, of which 12 had CKD due to congenital (<i>n</i> = 7) and perinatal (<i>n</i> = 5) causes. Plasma <span>d-</span>asparagine and the <span>d/l-</span>serine ratio had robust, positive linear associations with serum creatinine and cystatin C, and detected CKD with high sensitivity and specificity, uninfluenced by body size or biochemical parameters. In the animal study, kidney dysfunction increased plasma <span>d-</span>asparagine and the <span>d/l-</span>serine ratio, but dexamethasone treatment did not. Thus, plasma <span>d-</span>asparagine and the <span>d/l-</span>serine ratio can be useful markers for renal function in children.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic peptides for coronary artery diseases: in silico methods and current perspectives","authors":"Ayca Aslan,&nbsp;Selcen Ari Yuka","doi":"10.1007/s00726-024-03397-3","DOIUrl":"10.1007/s00726-024-03397-3","url":null,"abstract":"<div><p>Many drug formulations containing small active molecules are used for the treatment of coronary artery disease, which affects a significant part of the world’s population. However, the inadequate profile of these molecules in terms of therapeutic efficacy has led to the therapeutic use of protein and peptide-based biomolecules with superior properties, such as target-specific affinity and low immunogenicity, in critical diseases. Protein‒protein interactions, as a consequence of advances in molecular techniques with strategies involving the combined use of in silico methods, have enabled the design of therapeutic peptides to reach an advanced dimension. In particular, with the advantages provided by protein/peptide structural modeling, molecular docking for the study of their interactions, molecular dynamics simulations for their interactions under physiological conditions and machine learning techniques that can work in combination with all these, significant progress has been made in approaches to developing therapeutic peptides that can modulate the development and progression of coronary artery diseases. In this scope, this review discusses in silico methods for the development of peptide therapeutics for the treatment of coronary artery disease and strategies for identifying the molecular mechanisms that can be modulated by these designs and provides a comprehensive perspective for future studies.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting hair breakage in alopecia areata: the central role of dysregulated cysteine homeostasis","authors":"Wen Xu,&nbsp;Bo Xie,&nbsp;Dongfan Wei,&nbsp;Xiuzu Song","doi":"10.1007/s00726-024-03395-5","DOIUrl":"10.1007/s00726-024-03395-5","url":null,"abstract":"<div><p>In the initial stages of Alopecia Areata (AA), the predominance of hair breakage or exclamation mark hairs serves as vital indicators of disease activity. These signs are non-invasive and are commonly employed in dermatoscopic examinations. Despite their clinical salience, the underlying etiology precipitating this hair breakage remains largely uncharted territory. Our exhaustive review of the existing literature points to a pivotal role for cysteine—a key amino acid central to hair growth—in these mechanisms. This review will probe and deliberate upon the implications of aberrant cysteine metabolism in the pathogenesis of AA. It will examine the potential intersections of cysteine metabolism with autophagy, ferroptosis, immunity, and psychiatric manifestations associated with AA. Such exploration could illuminate new facets of the disease's pathophysiology, potentially paving the way for innovative therapeutic strategies.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11108903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of peptides for immunodiagnosis of human Chagas disease","authors":"Anna Julia Ribeiro,&nbsp;Kamila Alves Silva,&nbsp;Lucas da Silva Lopes,&nbsp;Carlos Ananias Aparecido Resende,&nbsp;Carolina Alves Petit Couto,&nbsp;Isadora Braga Gandra,&nbsp;Isabela Amorim Gonçalves Pereira,&nbsp;Isabelle Caroline Dos Santos Barcelos,&nbsp;Sabrina Paula Pereira,&nbsp;Sandra Rodrigues Xavier,&nbsp;Grasiele de Sousa Viera Tavares,&nbsp;Juliana Martins Machado,&nbsp;Mariana Campos Da Paz,&nbsp;Miguel Angel Chávez-Fumagalli,&nbsp;Eduardo Antonio Ferraz Coelho,&nbsp;Rodolfo Cordeiro Giunchetti,&nbsp;Ana Thereza Chaves,&nbsp;Walderez Ornelas Dutra,&nbsp;Ana Alice Maia Gonçalves,&nbsp;Alexsandro Sobreira Galdino","doi":"10.1007/s00726-024-03394-6","DOIUrl":"10.1007/s00726-024-03394-6","url":null,"abstract":"<div><p>Chagas disease, caused by the protozoa <i>Trypanosoma cruzi</i>, continues to be a serious public health problem in Latin America, worsened by the limitations in its detection. Given the importance of developing new diagnostic methods for this disease, the present review aimed to verify the number of publications dedicated to research on peptides that demonstrate their usefulness in serodiagnosis. To this end, a bibliographic survey was conducted on the PubMed platform using the keyword “peptide” or “epitope” combined with “Chagas disease” or “<i>Trypanosoma cruzi</i>”; “diagno*” or “serodiagnosis” or “immunodiagnosis”, without period restriction. An increasing number of publications on studies employing peptides in ELISA and rapid tests assays was verified, which confirms the expansion of research in this field. It is possible to observe that many of the peptides tested so far originate from proteins widely used in the diagnosis of Chagas, and many of them are part of commercial tests developed. In this sense, as expected, promising results were obtained for several peptides when tested in ELISA, as many of them exhibited sensitivity and specificity values above 90%. Furthermore, some peptides have been tested in several studies, confirming their diagnostic potential. Despite the promising results observed, it is possible to emphasize the need for extensive testing of peptides, using different serological panels, in order to confirm their potential. The importance of producing an effective assay capable of detecting the clinical stages of the disease, as well as new immunogenic antigens that enable new serological diagnostic tools for Chagas disease, is evident.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11065921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pDNA-tachyplesin treatment stimulates the immune system and increases the probability of apoptosis in MC4-L2 tumor cells","authors":"Fatemeh Mahmoudi-Filabadi,&nbsp;Abbas Doosti","doi":"10.1007/s00726-024-03393-7","DOIUrl":"10.1007/s00726-024-03393-7","url":null,"abstract":"<div><p>Breast cancer is the most common cancer among women worldwide, and marine creatures are the most abundant reservoir of anticancer medicines. Tachyplesin peptides have shown antibacterial capabilities, but their potential to inhibit cancer growth and trigger cancer cell death has not been investigated. A synthetic tachyplesin nucleotide sequence was generated and inserted into the pcDNA3.1( +) Mammalian Expression Vector. PCR analysis and enzyme digesting procedures were used to evaluate the vectors' accuracy. The transfection efficiency of MCF-7 and MCF10-A cells was 57% and 65%, respectively. The proliferation of MCF-7 cancer cells was markedly suppressed. Administration of plasmid DNA (pDNA) combined with tachyplesin to mice with tumors did not cause any discernible morbidity or mortality throughout treatment. The final body weight curves revealed a significant reduction in weight among mice treated with pDNA/tachyplesin and tachyplesin at a dose of 100 µg/ml (18.4 ± 0.24 gr, <i>P</i> &lt; 0.05; 11.4 ± 0.24 gr <i>P</i> &lt; 0.01) compared to the control group treated with PBS (22 ± 0.31 gr). Animals treated with pDNA/tachyplesin and tachyplesin exhibited a higher percentage of CD4 + Foxp3 + Tregs, CD8 + Foxp3 + Tregs, and CD4 + and CD8 + T cell populations expressing CTLA-4 in their lymph nodes and spleen compared to the PBS group. The groups that received pDNA/tachyplesin exhibited a substantial upregulation in the expression levels of caspase-3, caspase-8, BAX, PI3K, STAT3, and JAK genes. The results offer new possibilities for treating cancer by targeting malignancies using pDNA/tachyplesin and activating the mTOR and NFκB signaling pathways.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03393-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140842238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights into the potential binding sites of Cathepsin D using molecular modelling techniques","authors":"Subodh A. Kamble,&nbsp;Sagar S. Barale,&nbsp;Ali Abdulmawjood Mohammed,&nbsp;Sneha B. Paymal,&nbsp;Nitin M. Naik,&nbsp;Kailas D. Sonawane","doi":"10.1007/s00726-023-03367-1","DOIUrl":"10.1007/s00726-023-03367-1","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is the most prevalent type of dementia caused by the accumulation of amyloid beta (Aβ) peptides. The extracellular deposition of Aβ peptides in human AD brain causes neuronal death. Therefore, it has been found that Aβ peptide degradation is a possible therapeutic target for AD. CathD has been known to breakdown amyloid beta peptides. However, the structural role of CathD is not yet clear. Hence, for the purpose of gaining a deeper comprehension of the structure of CathD, the present computational investigation was performed using virtual screening technique to predict CathD's active site residues and substrate binding mode. Ligand-based virtual screening was implemented on small molecules from ZINC database against crystal structure of CathD. Further, molecular docking was utilised to investigate the binding mechanism of CathD with substrates and virtually screened inhibitors. Localised compounds obtained through screening performed by PyRx and AutoDock 4.2 with CathD receptor and the compounds having highest binding affinities were picked as; ZINC00601317, ZINC04214975 and ZINCC12500925 as our top choices. The hydrophobic residues Viz<i>.</i> Gly35, Val31, Thr34, Gly128, Ile124 and Ala13 help stabilising the CathD-ligand complexes, which in turn emphasises substrate and inhibitor selectivity. Further, MM-GBSA approach has been used to calculate binding free energy between CathD and selected compounds. Therefore, it would be beneficial to understand the active site pocket of CathD with the assistance of these discoveries. Thus, the present study would be helpful to identify active site pocket of CathD, which could be beneficial to develop novel therapeutic strategies for the AD.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-023-03367-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140676374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}