keyword
MENU ▼
Read by QxMD icon Read
search

Dpp9

keyword
https://www.readbyqxmd.com/read/29660786/activity-and-selectivity-cliffs-for-dpp-iv-inhibitors-lessons-we-can-learn-from-sar-studies-and-their-application-to-virtual-screening
#1
REVIEW
María José Ojeda-Montes, Aleix Gimeno, Sarah Tomas-Hernández, Adrià Cereto-Massagué, Raúl Beltrán-Debón, Cristina Valls, Miquel Mulero, Gerard Pujadas, Santiago Garcia-Vallvé
The inhibition of dipeptidyl peptidase-IV (DPP-IV) has emerged over the last decade as one of the most effective treatments for type 2 diabetes mellitus, and consequently (a) 11 DPP-IV inhibitors have been on the market since 2006 (three in 2015), and (b) 74 noncovalent complexes involving human DPP-IV and drug-like inhibitors are available at the Protein Data Bank (PDB). The present review aims to (a) explain the most important activity cliffs for DPP-IV noncovalent inhibition according to the binding site structure of DPP-IV, (b) explain the most important selectivity cliffs for DPP-IV noncovalent inhibition in comparison with other related enzymes (i...
April 16, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29426867/crystal-structures-of-a-bacterial-dipeptidyl-peptidase-iv-reveal-a-novel-substrate-recognition-mechanism-distinct-from-that-of-mammalian-orthologues
#2
Saori Roppongi, Yoshiyuki Suzuki, Chika Tateoka, Mayu Fujimoto, Saori Morisawa, Ippei Iizuka, Akihiro Nakamura, Nobuyuki Honma, Yosuke Shida, Wataru Ogasawara, Nobutada Tanaka, Yasumitsu Sakamoto, Takamasa Nonaka
Dipeptidyl peptidase IV (DPP IV, DPP4, or DAP IV) preferentially cleaves substrate peptides with Pro or Ala at the P1 position. The substrate recognition mechanism has been fully elucidated for mammalian DPP IV by crystal structure analyses but not for bacterial orthologues. Here, we report the crystal structures of a bacterial DPP IV (PmDAP IV) in its free form and in complexes with two kinds of dipeptides as well as with a non-peptidyl inhibitor at 1.90 to 2.47 Å resolution. Acyl-enzyme intermediates were observed for the dipeptide complexes of PmDAP IV, whereas tetrahedral intermediates were reported for the oligopeptide complexes of mammalian DPP IVs...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29396289/inhibition-of-dpp8-9-activates-the-nlrp1b-inflammasome
#3
Marian C Okondo, Sahana D Rao, Cornelius Y Taabazuing, Ashley J Chui, Sarah E Poplawski, Darren C Johnson, Daniel A Bachovchin
Val-boroPro (PT-100, Talabostat) induces powerful anti-tumor immune responses in syngeneic cancer models, but its mechanism of action has not yet been established. Val-boroPro is a non-selective inhibitor of post-proline-cleaving serine proteases, and the inhibition of the highly related cytosolic serine proteases Dpp8 and Dpp9 (Dpp8/9) by Val-boroPro was recently demonstrated to trigger an immunostimulatory form of programmed cell death known as pyroptosis selectively in monocytes and macrophages. Here we show that Dpp8/9 inhibition activates the inflammasome sensor protein Nlrp1b, which in turn activates pro-caspase-1 to mediate pyroptosis...
January 26, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29382749/structures-and-mechanism-of-dipeptidyl-peptidases-8-and-9-important-players-in-cellular-homeostasis-and-cancer
#4
Breyan Ross, Stephan Krapp, Martin Augustin, Reiner Kierfersauer, Marcelino Arciniega, Ruth Geiss-Friedlander, Robert Huber
Dipeptidyl peptidases 8 and 9 are intracellular N-terminal dipeptidyl peptidases (preferentially postproline) associated with pathophysiological roles in immune response and cancer biology. While the DPP family member DPP4 is extensively characterized in molecular terms as a validated therapeutic target of type II diabetes, experimental 3D structures and ligand-/substrate-binding modes of DPP8 and DPP9 have not been reported. In this study we describe crystal and molecular structures of human DPP8 (2.5 Å) and DPP9 (3...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28893231/involvement-of-dpp9-in-gene-fusions-in-serous-ovarian-carcinoma
#5
Marianne Lislerud Smebye, Antonio Agostini, Bjarne Johannessen, Jim Thorsen, Ben Davidson, Claes Göran Tropé, Sverre Heim, Rolf Inge Skotheim, Francesca Micci
BACKGROUND: A fusion gene is a hybrid gene consisting of parts from two previously independent genes. Chromosomal rearrangements leading to gene breakage are frequent in high-grade serous ovarian carcinomas and have been reported as a common mechanism for inactivating tumor suppressor genes. However, no fusion genes have been repeatedly reported to be recurrent driver events in ovarian carcinogenesis. We combined genomic and transcriptomic information to identify novel fusion gene candidates and aberrantly expressed genes in ovarian carcinomas...
September 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28887018/dpp9-enzyme-activity-controls-survival-of-mouse-migratory-tongue-muscle-progenitors-and-its-absence-leads-to-neonatal-lethality-due-to-suckling-defect
#6
Munkyung Kim, Maryline Minoux, Alessandro Piaia, Benjamin Kueng, Berangere Gapp, Delphine Weber, Corinne Haller, Samuel Barbieri, Kenji Namoto, Thorsten Lorenz, Johann Wirsching, Frederic Bassilana, William Dietrich, Filippo M Rijli, Iwona Ksiazek
Dipeptidyl peptidase 9 (DPP9) is an intracellular N-terminal post-proline-cleaving enzyme whose physiological function remains largely unknown. We investigated the role of DPP9 enzyme in vivo by characterizing knock-in mice expressing a catalytically inactive mutant form of DPP9 (S729A; DPP9(ki/ki) mice). We show that DPP9(ki/ki) mice die within 12-18h after birth. The neonatal lethality can be rescued by manual feeding, indicating that a suckling defect is the primary cause of neonatal lethality. The suckling defect results from microglossia, and is characterized by abnormal formation of intrinsic muscles at the distal tongue...
November 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28711492/species-specific-real-time-rt-pcr-analysis-of-expression-of-stromal-cell-genes-in-a-tumor-xenotransplantation-model-in-mice
#7
Evzen Krepela, Petr Busek, Marek Hilser, Zdislava Vanickova, Aleksi Sedo
Human tumor xenografts in mice together with the species-specific analysis of expressed genes allow to study the molecular processes driving tumor growth and progression in vivo and help to develop and evaluate anticancer therapies. In the present work, we designed and validated species-specific real-time RT-PCR assays for discrimination and quantitation of expression of human and mouse transcripts in cancer and stromal cells including dipeptidyl peptidase (DPP) 4, DPP8, DPP9, fibroblast activation protein (FAP) and CXC chemokine receptor 4 in mixed human-mouse biological samples...
September 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28507818/screening-of-a-natural-compound-library-identifies-emodin-a-natural-compound-from-rheum-palmatum-linn-that-inhibits-dpp4
#8
Zhaokai Wang, Longhe Yang, Hu Fan, Peng Wu, Fang Zhang, Chao Zhang, Wenjie Liu, Min Li
Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC50 of 5.76 µM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity...
2017: PeerJ
https://www.readbyqxmd.com/read/28392147/pyroptosis-and-apoptosis-pathways-engage-in-bidirectional-crosstalk-in-monocytes-and-macrophages
#9
Cornelius Y Taabazuing, Marian C Okondo, Daniel A Bachovchin
Pyroptosis is a lytic form of programmed cell death mediated by the inflammatory caspase-1, -4, and -5. We recently discovered that small-molecule inhibitors of the serine peptidases DPP8 and DPP9 (DPP8/9) induce pro-caspase-1-dependent pyroptosis in monocytes and macrophages. Notably, DPP8/9 inhibitors, unlike microbial agents, absolutely require caspase-1 to induce cell death. Therefore, DPP8/9 inhibitors are useful probes to study caspase-1 in cells. Here, we show that, in the absence of the pyroptosis-mediating substrate gasdermin D (GSDMD), caspase-1 activates caspase-3 and -7 and induces apoptosis, demonstrating that GSDMD is the only caspase-1 substrate that induces pyroptosis...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28256001/expression-subcellular-localisation-and-possible-roles-of-dipeptidyl-peptidase-9-dpp9-in-murine-macrophages
#10
Emilija Zapletal, Barbara Cupic, Jelka Gabrilovac
Dipeptidyl peptidase 9 (DPP9) is a peptidase of the DPPIV gene family, and its role in immune responses has been reported. In this study, we compared the messenger RNA expression profile of DPP9 to that of the related DPP8 and DPPIV in murine haematopoietic and lymphatic tissues. A similar order of expression levels was observed for all 3 peptidases: peritoneal macrophages < bone marrow < spleen ≤ lymph nodes. Also, we examined the subcellular localisation of DPP9 and its possible role(s) in J774 cell line of macrophage origin...
March 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/27943262/contribution-of-upregulated-dipeptidyl-peptidase-9-dpp9-in-promoting-tumoregenicity-metastasis-and-the-prediction-of-poor-prognosis-in-non-small-cell-lung-cancer-nsclc
#11
Zhiyuan Tang, Jun Li, Qin Shen, Jian Feng, Hua Liu, Wei Wang, Liqin Xu, Guanglin Shi, Xumei Ye, Min Ge, Xiaoyu Zhou, Songshi Ni
Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra-enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non-small-cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial-mesenchymal transition (EMT)...
April 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27820798/dpp8-and-dpp9-inhibition-induces-pro-caspase-1-dependent-monocyte-and-macrophage-pyroptosis
#12
Marian C Okondo, Darren C Johnson, Ramya Sridharan, Eun Bin Go, Ashley J Chui, Mitchell S Wang, Sarah E Poplawski, Wengen Wu, Yuxin Liu, Jack H Lai, David G Sanford, Michael O Arciprete, Todd R Golub, William W Bachovchin, Daniel A Bachovchin
Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. We demonstrate that the inhibition of two serine proteases, DPP8 and DPP9, activates the pro-protein form of caspase-1 independent of the inflammasome adaptor ASC...
January 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/27682012/dipeptidyl-peptidase-9-dpp9-in-human-skin-cells
#13
Jelka Gabrilovac, Barbara Čupić, Emilija Zapletal, Ognjen Kraus, Jasminka Jakić-Razumović
BACKGROUND: Dipeptidyl peptidase 9 (DPP9) is a relatively new member of the DPPIV family of prolyl dipeptidases which is ubiquitously expressed. Its role in regulation of immune responses and proliferation of epithelial carcinoma cells was reported. There is no data on possible role of DPP9 expressed in skin epithelial cells (keratinocytes) and in dermal fibroblasts. MATERIALS AND METHODS: Transcriptional and protein expression of DPP9 and DPPIV was examined in fibroblasts and keratinocytes isolated from normal human skin...
February 2017: Immunobiology
https://www.readbyqxmd.com/read/27614019/dpp9-is-a-novel-component-of-the-n-end-rule-pathway-targeting-the-tyrosine-kinase-syk
#14
Daniela Justa-Schuch, Maria Silva-Garcia, Esther Pilla, Michael Engelke, Markus Kilisch, Christof Lenz, Ulrike Möller, Fumihiko Nakamura, Henning Urlaub, Ruth Geiss-Friedlander
The aminopeptidase DPP9 removes dipeptides from N-termini of substrates having a proline or alanine in second position. Although linked to several pathways including cell survival and metabolism, the molecular mechanisms underlying these outcomes are poorly understood. We identified a novel interaction of DPP9 with Filamin A, which recruits DPP9 to Syk, a central kinase in B-cell signalling. Syk signalling can be terminated by degradation, requiring the ubiquitin E3 ligase Cbl. We show that DPP9 cleaves Syk to produce a neo N-terminus with serine in position 1...
September 10, 2016: ELife
https://www.readbyqxmd.com/read/27410463/dipeptidyl-peptidase-9-substrates-and-their-discovery-current-progress-and-the-application-of-mass-spectrometry-based-approaches
#15
REVIEW
Claire H Wilson, Hui Emma Zhang, Mark D Gorrell, Catherine A Abbott
The enzyme members of the dipeptidyl peptidase 4 (DPP4) gene family have the very unusual capacity to cleave the post-proline bond to release dipeptides from the N-terminus of peptide/protein substrates. DPP4 and related enzymes are current and potential therapeutic targets in the treatment of type II diabetes, inflammatory conditions and cancer. Despite this, the precise biological function of individual dipeptidyl peptidases (DPPs), other than DPP4, and knowledge of their in vivo substrates remains largely unknown...
September 1, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/26930324/dipeptidyl-peptidase-9-enzymatic-activity-influences-the-expression-of-neonatal-metabolic-genes
#16
Yiqian Chen, Margaret G Gall, Hui Zhang, Fiona M Keane, Geoffrey W McCaughan, Denise M T Yu, Mark D Gorrell
The success of dipeptidyl peptidase 4 (DPP4) inhibition as a type 2 diabetes therapy has encouraged deeper examination of the post-proline DPP enzymes. DPP9 has been implicated in immunoregulation, disease pathogenesis and metabolism. The DPP9 enzyme-inactive (Dpp9 gene knock-in; Dpp9 gki) mouse displays neonatal lethality, suggesting that DPP9 enzyme activity is essential in neonatal development. Here we present gene expression patterns in these Dpp9 gki neonatal mice. Taqman PCR arrays and sequential qPCR assays on neonatal liver and gut revealed differential expression of genes involved in cell growth, innate immunity and metabolic pathways including long-chain-fatty-acid uptake and esterification, long-chain fatty acyl-CoA binding, trafficking and transport into mitochondria, lipoprotein metabolism, adipokine transport and gluconeogenesis in the Dpp9 gki mice compared to wild type...
March 1, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/26671446/unravelling-the-immunological-roles-of-dipeptidyl-peptidase-4-dpp4-activity-and-or-structure-homologue-dash-proteins
#17
REVIEW
L Wagner, C Klemann, M Stephan, S von Hörsten
Dipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins...
June 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/26579375/establishment-of-a-selective-evaluation-method-for-dpp4-inhibitors-based-on-recombinant-human-dpp8-and-dpp9-proteins
#18
Jinglong Liu, Yi Huan, Caina Li, Minzhi Liu, Zhufang Shen
Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy...
April 2014: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/26454447/the-dipeptidyl-peptidases-4-8-and-9-in-mouse-monocytes-and-macrophages-dpp8-9-inhibition-attenuates-m1-macrophage-activation-in-mice
#19
Yannick Waumans, Gwendolyn Vliegen, Lynn Maes, Miche Rombouts, Ken Declerck, Pieter Van Der Veken, Wim Vanden Berghe, Guido R Y De Meyer, Dorien Schrijvers, Ingrid De Meester
Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation...
February 2016: Inflammation
https://www.readbyqxmd.com/read/26300881/the-dipeptidyl-peptidase-family-prolyl-oligopeptidase-and-prolyl-carboxypeptidase-in-the-immune-system-and-inflammatory-disease-including-atherosclerosis
#20
REVIEW
Yannick Waumans, Lesley Baerts, Kaat Kehoe, Anne-Marie Lambeir, Ingrid De Meester
Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases...
2015: Frontiers in Immunology
keyword
keyword
95449
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"