Ask about this productRelated genes to: KLK11 antibody
- Gene:
- KLK11 NIH gene
- Name:
- kallikrein related peptidase 11
- Previous symbol:
- PRSS20
- Synonyms:
- TLSP
- Chromosome:
- 19q13.41
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-19
- Date modifiied:
- 2016-11-15
Related products to: KLK11 antibody
Related articles to: KLK11 antibody
- Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of inflammatory responses in asthma, allergy and other diseases. Here we report an anti-β-tryptase antibody with a superior mechanism of action compared to others since it not only inhibits tetrameric β-tryptase, but also completely inhibits monomeric β-tryptase activity. The antibody binds to an exosite that causes tetramer dissociation as either an IgG or Fab and, in addition, allosterically alters the substrate binding cleft on monomers, thus preventing substrate binding and proteolysis. We solve the cryoEM structure of the complex, generate biochemical data and engineer point mutations to elucidate the allosteric path of inhibition. This ultimately reveals a single Asp to Gly mutation in CDR-L3 that only slightly impacts binding affinity, but completely eliminates inhibitory activity. Finally, we improve antibody inhibitory potency up to 4.7-fold by structure-based design creating new charge-charge interactions. This antibody may have enhanced efficacy and potential to assess the relevance of β-tryptase, including monomers, in biological and clinical settings. - Source: PubMed
Publication date: 2026/04/09
Maun Henry RAzumaya Caleigh MWalters Benjamin TVij RajeshMorando AshleyLoyet Kelly MKoerber James TRohou AlexisLazarus Robert A - High temperature requirement protein A1 (HTRA1) is a trypsin-like serine protease increasingly recognized as a central regulator of brain homeostasis. HTRA1 is broadly expressed in the brain, where it regulates proteostasis, extracellular matrix (ECM) remodeling, and important signaling pathways such as TGF-β, Wnt, and Notch. These functions are essential for maintaining blood-brain barrier integrity, supporting tissue repair, and restraining inflammation. HTRA1 is a double-edged sword, as both insufficient and excessive activity can lead to neurodegenerative and vascular pathology. Reduced HTRA1 levels are linked to ECM accumulation and vascular fibrosis, while elevated activity contributes to tissue breakdown, inflammation, and impaired repair. This dual role is implicated in a range of disorders, including cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, small vessel disease, age-related macular degeneration, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We review recent insights into HTRA1's interactions with ApoE and tau, its roles in lipid and cytoskeletal regulation, and its modulation by inhibitors such as Macrophage Migration Inhibitory Factor. Finally, we explore its biomarker potential and therapeutic targeting strategies. Understanding the mechanisms behind HTRA1's shift from protective to pathological is crucial for developing targeted therapies that preserve its beneficial roles. - Source: PubMed
Publication date: 2026/04/01
Hjæresen SimoneGramkow Emilie TrommerZhang MengliangFex Svenningsen Åsa - High myopia (HM), characterized by significant ocular axial length elongation, affects hundreds of millions of people and is often inherited, particularly in cases that develop during childhood or adolescence. Although numerous myopia loci (MYP) have been identified, most causative genes remain undefined. Here, we analyzed two large HM pedigrees and refined the critical region through haplotype linkage analysis to a 3.9-Mb interval on 2q37.1, which was previously reported as MYP12 with an unknown pathogenic gene. Whole-genome sequencing identified the noncoding promoter variants c.-187G>T and c.-187G>C in PRSS56, encoding a trypsin-like serine protease, which exclusively co-segregated with all affected members in both pedigrees. Compared with matched controls, increased PRSS56 expression was observed in both patient-derived iPSCs carrying c.-187G>T and knock-in mice (c.-155G>T, corresponding to human c.-187G>T) that faithfully recapitulate myopia phenotypes. Noncoding PRSS56 variants promote self-expression via enhanced binding to the transcription factor EGR1, as confirmed by dual-luciferase assays. Notably, we demonstrated that higher PRSS56 levels directly increase ocular axial length in a dose- and activity-dependent manner in multiple transgenic mouse models. Guinea pig myopia models consistently exhibited high Prss56 expression, and short-wave light exposure reduced Prss56 mRNA levels and attenuated further axial elongation. Mechanistically, higher PRSS56 expression was associated with reduced abundance of myosin-4 in the sclera and with molecular signatures of scleral remodeling, which were in turn correlated with axial elongation. In conclusion, our findings provide strong genetic and functional evidence for the pathogenic role of noncoding PRSS56 variants in HM and highlight PRSS56 as a promising therapeutic target for juvenile HM. - Source: PubMed
Publication date: 2026/04/01
Wu BoxuanZeng WeijiaTang KefuXiong JiaweiMo XiaofenFu QingFu DanChu RenyuanZhao GuoliLu LeiWang ZhongfengWu LingqianYu ZhiqiangZhou XiangyuWang Hongyan - is a trypsin-like serine protease that has emerged as a regulator of DNA replication, and is directly related to genome stability, protein homeostasis, antiviral defense and cancer progression. Pathogenic variants in are correlated with genetic syndromes such as Kenny-Caffey syndrome type 2 (KCS2) and gracile bone dysplasia/osteocraniostenosis (GCLEB/OCS). This study focuses on the evolutionary, genetic, and structural analysis of , in order to identify key regions and candidate pharmacological targets that are related to this enzyme's function. The methodology of this in silico study includes separate analyses at the sequence, structural and functional levels. Initially, data mining was carried out using NCBI/Protein (2025), and then data filtering was performed in order to identify representative FAM111A sequences for several species. Sequence analysis was then executed through multiple alignments and phylogenetic analyses. Through this, conserved domains and motifs were identified. For structural analysis, human pathogenic mutations and protein structures were identified through searches in biological databases including PDB and ClinVar, and then all data were analyzed in order to identify candidate pharmacological targets related to function. Approximately 1850 FAM111A protein sequences were retrieved for several species, and after filtering processes a dataset of 85 representative sequences was generated. Evolutionary analysis indicates that FAM111A originated in early metazoans, with progressive domain specialization leading to mammal-restricted acquisition of regulatory elements, including the PIP-box PCNA (proliferating cell nuclear antigen) interacting peptide and UBL (ubiquitin-like) domains. The ubiquitin-like/DNA binding domain and catalytic serine protease domain (SPD) are the most conserved, containing seven highly conserved motifs. The structural analysis was based on two protein structures and 34 critical mutations that accumulate in two distinct regions. Finally, by combining the results, six pharmacological targets and 100 inhibitors are proposed. Advancing the structural and function characterization of FAM111A, coupled with pharmacological target identification and evolutionary insights, will be critical to validate this underexplored protease as a therapeutic genetic target in genetic disorders, cancer, and antiviral responses. - Source: PubMed
Publication date: 2026/02/27
Hatziagapiou KyriakiKarachaliou FeneliThireou TriasKoniari EleniChaniotis DimitriosBeloukas ApostolosStathori GalateiaKafkaloudi PanagiotaKrumbholz BettinaChrousos George PPapageorgiou Louis - Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae) is a major agricultural pest whose control has been increasingly challenged by resistance to conventional insecticides. Synthetic protease inhibitors represent promising alternatives; however, the potential modulation of their efficacy by gut microbiota remains poorly understood. Here, we evaluated two rationally designed synthetic tripeptides, GORE1 and GORE2, as inhibitors of trypsin-like digestive proteases and investigated whether gut microbiota disruption alters their inhibitory performance in S. frugiperda. Enzymatic assays revealed competitive inhibition patterns, with K values of 1.41 mM for GORE1 and 0.49 mM for GORE2. Most treatments increased apparent K values, indicating reduced substrate affinity, whereas GORE2 consistently showed lower K values. Despite stronger in vitro affinity (lower K), GORE2 did not produce greater biological impairment than GORE1. Microbiota imbalance induced by antibiotic treatment did not significantly alter larval survival or enzymatic inhibition patterns but modulated specific developmental responses, particularly prolonged larval development and reduced body mass under GORE1 exposure. Nutritional indices (ECI and ECD) were significantly reduced in peptide-treated larvae, supporting impaired protein metabolism. These findings demonstrate that synthetic peptides effectively inhibit trypsin-like proteases in S. frugiperda and negatively affect larval nutritional performance. Although microbiota disruption did not modify survival or primary enzymatic inhibition, microbiota-mediated compensatory mechanisms cannot be excluded. Future integrative studies combining microbiome profiling and metabolic analyses will be essential to resolve host-enzyme-microbiota interactions under digestive inhibition. - Source: PubMed
Schultz HalinaPaulo Daniel Guimarães SilvaMeriño-Cabrera Yaremisde Andrade Rafael JúniorSantos Ian Lucas BatistaRodrigues Maria Clara Neves GomesMariano Geisiane AparecidaLima Milena Godoide Oliveira Humberto Josué RamosOliveira Maria Goreti de Almeida