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ORCID Profile
Orcid icon. 0000-0002-7721-6657

Current Organisations
Goethe University Frankfurt , Applied Science Private University Faculty of Pharmacy , Applied Science Private University

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Publications

Publication

The era of E-learning from the perspectives of Jordanian medical students: A cross-sectional study

Publisher: Elsevier BV

Date: 07-2022

DOI: 10.1016/J.HELIYON.2022.E09928

Publication

Legionella pneumophilamacrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding

Publisher: Cold Spring Harbor Laboratory

Date: 26-04-2023

DOI: 10.1101/2023.04.24.538046

Abstract: Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila , the causative agent of Legionnaires’ disease and protozoans such as Trypanosoma cruzi . All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl- cis/trans - isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella pneumophila protein ( Lp MIP) have additional appendage domains of mostly unknown function. In full- length, homodimeric Lp MIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of Lp MIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of Lp MIP and Tc MIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms.

Publication

Legionella pneumophila macrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding

Publisher: Elsevier BV

Date: 12-2023

Location: No location found

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Related Funding Activities

No related grants have been discovered for Benedikt Goretzki.

Benedikt Goretzki

Researcher

Related Links

Publications

The era of E-learning from the perspectives of Jordanian medical students: A cross-sectional study

Legionella pneumophilamacrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding

Legionella pneumophila macrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding

Related Organisations

Goethe University Frankfurt

University Of Jordan

Applied Science Private University Faculty Of Pharmacy

Applied Science Private University

Queen's University Of Belfast School Of Pharmacy

Johannes-Gutenberg-University

Johannes Gutenberg-Universität Mainz

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