Aymelt Itzen

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Organization: Technische Universit?t München , Germany

Department: Chemistry Department

Title: Professor(PhD)

Chemicals
References

AMP-Modifikationen als Strategien bakterieller Krankheitserreger

Co-reporter:Aymelt Itzen

BIOspektrum 2016 Volume 22( Issue 4) pp:359-361

Publication Date(Web):2016 June

DOI:10.1007/s12268-016-0697-9

Bacterial pathogens have evolved with enzyme activities that may hijack intracellular signaling of mammalian cells to establish an infection. Of particular interest is a novel posttranslational modification referred to as adenylylation: An adenosine monophosphate group is covalently transferred to a mammalian target protein. Here, I discuss the consequences of adenylylation and its related modifications by Fic enzymes. Also, I comment on potential applications for protein labeling.

Molecular Perspectives on Protein Adenylylation

Co-reporter:Christian Hedberg and Aymelt Itzen

ACS Chemical Biology 2015 Volume 10(Issue 1) pp:12

Publication Date(Web):December 8, 2014

DOI:10.1021/cb500854e

In the cell, proteins are frequently modified covalently at specific amino acids with post-translational modifications, leading to a diversification of protein functions and activities. Since the introduction of high-resolution mass spectrometry, new post-translational modifications are constantly being discovered. One particular modification is the adenylylation of mammalian proteins. In adenylylation, adenosine triphosphate (ATP) is utilized to attach an adenosine monophosphate at protein threonine or tyrosine residues via a phosphodiester linkage. Adenylylation is particularly interesting in the context of infections by bacterial pathogens during which mammalian proteins are manipulated through AMP attachment via secreted bacterial factors. In this review, we summarize the role and regulation of enzymatic adenylylation and the mechanisms of catalysis. We also refer to recent methods for the detection of adenylylated proteins by modification-specific antibodies, ATP analogues equipped with chemical handles, and mass spectrometry approaches. Additionally, we review screening approaches for inhibiting adenylylation and briefly discuss related modifications such as phosphocholination and phosphorylation.

Covalent Protein Labeling by Enzymatic Phosphocholination

Co-reporter:M.Sc. Katharina Heller;M.Sc. Philipp Ochtrop;M.Sc. Michael F. Albers;Florian B. Zauner;Dr. Aymelt Itzen;Dr. Christian Hedberg

Angewandte Chemie International Edition 2015 Volume 54( Issue 35) pp:10327-10330

Publication Date(Web):

DOI:10.1002/anie.201502618

Abstract

We present a new protein labeling method based on the covalent enzymatic phosphocholination of a specific octapeptide amino acid sequence in intact proteins. The bacterial enzyme AnkX from Legionella pneumophila has been established to transfer functional phosphocholine moieties from synthetically produced CDP-choline derivatives to N-termini, C-termini, and internal loop regions in proteins of interest. Furthermore, the covalent modification can be hydrolytically removed by the action of the Legionella enzyme Lem3. Only a short peptide sequence (eight amino acids) is required for efficient protein labeling and a small linker group (PEG-phosphocholine) is introduced to attach the conjugated cargo.

Kovalente Proteinmarkierung durch enzymatische Phosphocholinierung

Co-reporter:M.Sc. Katharina Heller;M.Sc. Philipp Ochtrop;M.Sc. Michael F. Albers;Florian B. Zauner;Dr. Aymelt Itzen;Dr. Christian Hedberg

Angewandte Chemie 2015 Volume 127( Issue 35) pp:10467-10471

Publication Date(Web):

DOI:10.1002/ange.201502618

Abstract

Wir präsentieren eine neue Methode zur Proteinmarkierung, die auf der kovalenten enzymatischen Phosphocholinierung einer spezifischen Octapeptidsequenz intakter Proteine beruht. Das Enzym AnkX aus Legionellen wurde etabliert, um funktionalisierte Phosphocholingruppen aus synthetischen CDP-Cholin-Derivaten auf N- und C-Termini, sowie interne Schleifenregionen zu übertragen. Zudem kann die kovalente Modifikation durch das Legionellen-Enzym Lem3 hydrolytisch entfernt werden. Lediglich eine 8 Aminosäuren kurze Peptidsequenz und eine kleine Verbindungsgruppe (PEG-Phosphocholin) sind für die effiziente Proteinmarkierung erforderlich.

Exploring Adenylylation and Phosphocholination as Post-Translational Modifications

Co-reporter:Dr. Matthias P. Müller;Michael F. Albers; Dr. Aymelt Itzen;Dr. Christian Hedberg

ChemBioChem 2014 Volume 15( Issue 1) pp:19-26

Publication Date(Web):

DOI:10.1002/cbic.201300508

The structure of the N-terminal domain of the Legionella protein SidC

Co-reporter:Emerich Mihai Gazdag, Stefan Schöbel, Alexander V. Shkumatov, Roger S. Goody, Aymelt Itzen

Journal of Structural Biology (April 2014) Volume 186(Issue 1) pp:188-194

Publication Date(Web):1 April 2014

DOI:10.1016/j.jsb.2014.02.003

The Gram-negative bacterium Legionella pneumophila is the causative agent of Legionnaires’ disease. During infection of eukaryotic cells, the bacterium releases about 300 different bacterial effector molecules that aid in the establishment of the Legionella-containing vacuole (LCV) among which SidC is one of these secreted proteins. However, apart from membrane lipid binding the function of SidC remains elusive. In order to characterize SidC further, we have determined the crystal structure of the N-terminal domain of SidC (amino acids 1–609, referred to as SidC-N) at 2.4 Å resolution. SidC-N reveals a novel fold in which 4 potential subdomains (A–D) are arranged in a crescent-like structure. None of these subdomains currently has any known structural homologues, raising the question of how this fold has evolved. These domains are highly interconnected, with a low degree of flexibility towards each other. Due to the extended arrangement of the subdomains, SidC-N may contain multiple binding sites for potential interaction partners.