---
title: "Fragment screening by X-ray crystallography identifies dynamic ligand-binding sites in M. tubercul"
id: "biorxiv-18-x-ray-crystallographic-fragment-screening-reveals-novel-and-conformationally"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-18-x-ray-crystallographic-fragment-screening-reveals-novel-and-conformationally"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.01.748605v1?rss=1"
published_at: "2026-09-02T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fragment screening by X-ray crystallography identifies dynamic ligand-binding sites in M. tubercul
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-18-x-ray-crystallographic-fragment-screening-reveals-novel-and-conformationally
- **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/10.64898/2026.09.01.748605v1?rss=1)
- **Published At:** 2026-09-02T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Tuberculosis remains a leading global infectious cause of death, creating an ongoing need for new mechanisms to inhibit Mycobacterium tuberculosis (Mtb). - **FtsZ**, a bacterial **GTPase** essential for cell division that assembles into protofilaments at the division site, is highlighted as an attractive drug target. - The authors performed an X-ray crystallographic **fragment screening** campaign against MtbFtsZ to identify potential ligand-binding pockets amenable to chemical elaboration. - In total, 1,070 crystals were soaked with fragment compounds; 714 diffraction datasets were passed to downstream analysis. - PanDDA (a multi-dataset density analysis tool) generated event maps; 149 datasets showed event-map density supporting modeling of fragment binding. - From the screen, the authors describe **15 novel ligand-binding sites** on MtbFtsZ. - Both conformational states of FtsZ reported in the study — the **ON** and the **OFF** conformations — were present together in the asymmetric unit of the crystal structures. - The data reveal asymmetric binding of fragments to each chain in the crystallographic model, indicating conformationally specific or chain-specific ligand interactions. - The crystallographic fragment hits offer starting points for fragment growing and fragment merging strategies to develop FtsZ binders into drug-like molecules or conformation-specific chemical probes. - The work is presented as a preprint and has not been peer reviewed; funding sources include the NIH and U.S. Department of Energy.
## Clinical Analysis & Structured Key Points
X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ | bioRxiv Skip to main content New Results X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ View ORCID Profile Kaylen R Meeks , View ORCID Profile Edwin O Lazo , View ORCID Profile Dale F Kreitler doi: https://doi.org/10.64898/2026.09.01.748605 Kaylen R Meeks Brookhaven National Laboratory Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kaylen R Meeks Edwin O Lazo Brookhaven National Laboratory Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Edwin O Lazo Dale F Kreitler Brookhaven National Laboratory Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dale F Kreitler For correspondence: dkreitler{at}bnl.gov Abstract Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Tuberculosis is a leading cause of death globally due to an infectious agent. There is ongoing need for novel mechanisms to inhibit M. tuberculosis (Mtb) growth and infection to improve patient outcomes. FtsZ, a GTPase that assembles into protofilaments at the division site of a replicating cell to produce two individual cells, is an attractive target as an essential protein in bacterial cell division. Here we describe a crystallographic fragment screening campaign of MtbFtsZ. 1,070 crystals were soaked with fragments and 714 datasets were used for downstream PanDDA analysis. 149 datasets exhibited PanDDA-generated event map density to support modeling of fragment binding. 15 novel sites are described. Both the ON and the OFF conformations of FtsZ are found in the asymmetric unit. Asymmetric binding of fragments to each chain in the model is observed. These crystallographic fragment screening results additionally provide opportunities for fragment growing and merging to develop FtsZ binders into drug-like molecules or conformation specific chemical probes. Competing Interest Statement The authors have declared no competing interest. Footnotes https://rcsb.org/groups/summary/entry/G_1002379 Funder Information Declared National Institutes of Health , P30GM133893 United States Department of Energy, https://ror.org/01bj3aw27 , KP1607011 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. Back to top Previous Next Posted September 02, 2026. Download PDF Supplementary Material Data/Code 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. 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Share X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ Kaylen R Meeks , Edwin O Lazo , Dale F Kreitler bioRxiv 2026.09.01.748605; doi: https://doi.org/10.64898/2026.09.01.748605 Share This Article: Copy Citation Tools X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ Kaylen R Meeks , Edwin O Lazo , Dale F Kreitler bioRxiv 2026.09.01.748605; doi: https://doi.org/10.64898/2026.09.01.748605 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 (7953) Biochemistry (18602) Bioengineering (14744) Bioinformatics (44050) Biophysics (22431) Cancer Biology (19557) Cell Biology (26708) Clinical Trials (138) Developmental Biology (13874) Ecology (20842) Epidemiology (2067) Evolutionary Biology (25267) Genetics (16084) Genomics (23365) Immunology (18560) Microbiology (42156) Molecular Biology (17924) Neuroscience (92702) Paleontology (693) Pathology (2964) Pharmacology and Toxicology (5054) Physiology (8040) Plant Biology (15881) Scientific Communication and Education (2090) Synthetic Biology (4532) Systems Biology (10168) Zoology (2371)
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