---
title: "Caspofungin binds the glucan exit portal of Nakaseomyces glabratus Fks1, structural analysis"
id: "biorxiv-5-structural-basis-of-caspofungin-inhibition-of-nakaseomyces-glabratus-fks1"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-5-structural-basis-of-caspofungin-inhibition-of-nakaseomyces-glabratus-fks1"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.21.760291v1?rss=1"
published_at: "2026-10-23T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Caspofungin binds the glucan exit portal of Nakaseomyces glabratus Fks1, structural analysis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-5-structural-basis-of-caspofungin-inhibition-of-nakaseomyces-glabratus-fks1
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.21.760291v1?rss=1)
- **Published At:** 2026-10-23T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators reported the resting-state structures of **Fks1** from Nakaseomyces glabratus in both apo and **caspofungin**-bound forms. - The drug was observed at the extracellular glucan exit portal, adjacent to the product **β-1,3-D-glucan**, in a position similar to that previously reported for S. cerevisiae Fks1. - The cohort showed absence of detectable **Rho1** binding in NgFks1, a difference from S. cerevisiae that may affect regulation. - Data indicated the glucan channel at resistance hotspot regions adopts an open-like conformation while the lower gate remains closed. - Authors noted that the closed lower gate suggests a molecule of glucan is trapped from a prior catalytic cycle, rather than an empty translocation path. - The study team observed that **caspofungin** can engage Fks1 in the absence of **Rho1**, implying potential species-specific differences in substrate movement, inhibition mechanisms, and routes to resistance. - The source did not report detailed experimental methods, such as resolution metrics, preparation conditions, or precise structural determination techniques, in the abstract. - Authors declared no competing interests and listed National Institute of Allergy and Infectious Diseases funding (NIH R01 AI156270).
## Clinical Analysis & Structured Key Points
Structural basis of caspofungin inhibition of Nakaseomyces glabratus Fks1 | bioRxiv Skip to main content New Results Structural basis of caspofungin inhibition of Nakaseomyces glabratus Fks1 Md Shamiul Islam Rasel , Darpan Raghav , Fahrin Jahan Suchana , Rodolpho Souza Amado de Carvalho , Thomas M Tomasiak doi: https://doi.org/10.64898/2026.10.21.760291 Md Shamiul Islam Rasel University of Arizona Find this author on Google Scholar Find this author on PubMed Search for this author on this site Darpan Raghav University of Arizona Find this author on Google Scholar Find this author on PubMed Search for this author on this site Fahrin Jahan Suchana University of Arizona Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rodolpho Souza Amado de Carvalho University of Arizona Find this author on Google Scholar Find this author on PubMed Search for this author on this site Thomas M Tomasiak University of Arizona Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: tomasiak{at}email.arizona.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract The Fks1 catalytic subunit of fungal glucan synthase crosslinks UDP-glucose into β-1,3-D-glucan in the fungal cell wall and is a target for the echinocandin class of antifungal drugs. Here, we present the resting state of Fks1 from Nakaseomyces glabratus (NgFks1) in both apo and caspofungin-bound states. Caspofungin binds the extracellular glucan exit portal of Fks1 adjacent to the product β-1,3-D-glucan in a position similar to that reported for S. cerevisiae Fks1. Unlike S. cerevisiae Fks1, no Rho1 binding is present, but the glucan channel opening is in an open-like state at the resistance hotspot regions. However, the lower gate is closed, suggesting glucan is trapped from a previous round of catalysis. Our results show that caspofungin can bind in a mode in the absence of Rho1 in N. glabratus and point to possible species-specific differences in substrate translocation, inhibition, and resistance mechanisms. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of Allergy and Infectious Diseases , NIH R01 AI156270 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted October 23, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Structural basis of caspofungin inhibition of Nakaseomyces glabratus Fks1 Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Structural basis of caspofungin inhibition of Nakaseomyces glabratus Fks1 Md Shamiul Islam Rasel , Darpan Raghav , Fahrin Jahan Suchana , Rodolpho Souza Amado de Carvalho , Thomas M Tomasiak bioRxiv 2026.10.21.760291; doi: https://doi.org/10.64898/2026.10.21.760291 Share This Article: Copy Citation Tools Structural basis of caspofungin inhibition of Nakaseomyces glabratus Fks1 Md Shamiul Islam Rasel , Darpan Raghav , Fahrin Jahan Suchana , Rodolpho Souza Amado de Carvalho , Thomas M Tomasiak bioRxiv 2026.10.21.760291; doi: https://doi.org/10.64898/2026.10.21.760291 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8164) Biochemistry (19027) Bioengineering (15171) Bioinformatics (45326) Biophysics (22958) Cancer Biology (20108) Cell Biology (27295) Clinical Trials (138) Developmental Biology (14143) Ecology (21395) Epidemiology (2067) Evolutionary Biology (25782) Genetics (16342) Genomics (23827) Immunology (19017) Microbiology (43180) Molecular Biology (18338) Neuroscience (95043) Paleontology (712) Pathology (3031) Pharmacology and Toxicology (5197) Physiology (8279) Plant Biology (16267) Scientific Communication and Education (2115) Synthetic Biology (4644) Systems Biology (10383) Zoology (2426)
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