Michael Henzl, PhD

Professor Emeritus


Contact Information

Email HenzlM@missouri.edu
Phone 573-882-7485
Address 11C Schlundt Annex


BS Chemistry Lafayette College Easton, Penn.
PhD Biochemistry University of Wisconsin Madison, Wis.

Research Area

Biophysical characterization of EF-hand calcium-binding proteins; protein-ligand interactions.

Research Description

My research interests are focused on protein-ligand interactions and their impact on protein structure and stability. The work has largely centered on select members of the “EF-hand” family. These proteins, which play important roles in eukaryotic signal transduction, are named for their characteristic Ca2+-binding site. Although these 30-residue motifs, consisting of a central binding loop and short flanking helices, share a general similarity, they vary widely in their affinity for Ca2+ and Mg2+. The lab has sought to identify the basis for this variation, using the parvalbumins — small vertebrate-specific proteins, harboring two Ca2+-binding sites — as a model system. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) figure prominently in this effort. Structural data obtained by X-ray crystallography or NMR spectroscopy assist with interpretation of the thermodynamic data.

In recent years, attention in the lab has turned to a protein called ALG-2, short for Apoptosis-Linked Gene 2. Whereas the parvalbumins are Ca2+ buffers, serving to modulate the amplitude and duration of Ca2+ signals in the cell, ALG-2 is a Ca2+ sensor. Upon binding Ca2+, following an increase in the intracellular Ca2+ level, it exposes a hydrophobic surface for interaction with biological targets. A dimeric protein, ALG-2 can simultaneous associate with two target proteins, prompting speculation that it functions as a molecular adaptor — stabilizing weak protein-protein complexes or linking two distinct proteins. ALG-2 has been implicated in several important processes — notably ER-Golgi vesicular transport, endosomal biogenesis and transport, and cell-membrane repair. A recent calorimetric investigation by this lab revealed that one of the EF-hand motifs in ALG-2 is Mg2+-specific at physiologically relevant levels of Ca2+ and Mg2+. A subsequent X-ray diffraction study, performed in collaboration with Dr. Tanner, identified the C-terminal EF-hand motif as the Mg2+-specific site. More recently, we have demonstrated that the ALG-2 dimerization reaction is modulated by the binding of Ca2+ and Mg2+ or target-protein surrogates.

Notable Honors and Service

  • Chair, 60th Calorimetry Conference, 2005
  • Scientific Program Chair, 59th Calorimetry Conference, 2004

Selected Publications

Henzl MT. (2018). Ligation events influence ALG-2 dimerization. Biophys Chem. 239:16-28. doi: 10.1016/j.bpc.2018.05.001. [PubMed]

Srivastava D, Razzaghi M, Henzl MT, Dey M. (2017). Structural Investigation of a Dimeric Variant of Pyruvate Kinase Muscle Isoform 2. Biochemistry. 56(50):6517-6520. doi: 10.1021/acs.biochem.7b01013. [PubMed]

Korasick DA, Wyatt JW, Luo M, Laciak AR, Ruddraraju K, Gates KS, Henzl MT, Tanner JJ. (2017). Importance of the C-Terminus of Aldehyde Dehydrogenase 7A1 for Oligomerization and Catalytic Activity. Biochemistry. 56(44):5910-5919. doi: 10.1021/acs.biochem.7b00803. [PubMed]

Korasick DA, Gamage TT, Christgen S, Stiers KM, Beamer LJ, Henzl MT, Becker DF, Tanner JJ. (2017). Structure and characterization of a class 3B proline utilization A: Ligand-induced dimerization and importance of the C-terminal domain for catalysis. J Biol Chem. 292(23):9652-9665. doi: 10.1074/jbc.M117.786855. [PubMed]

Korasick DA, Tanner JJ, Henzl MT. (2017). Impact of disease-Linked mutations targeting the oligomerization interfaces of aldehyde dehydrogenase 7A1. Chem Biol Interact. 276:31-39. doi: 10.1016/j.cbi.2017.01.002. [PubMed]

Tanner JJ, Frey BB, Pemberton T, Henzl MT. (2016). EF5 Is the High-Affinity Mg(2+) Site in ALG-2. Biochemistry. 55(36):5128-41. doi: 10.1021/acs.biochem.6b00596. [PubMed]

Henzl MT, Frey BB, Wolf AJ. (2016). ALG-2 divalent-ion affinity: Calorimetric analysis of the des23 versions reveals high-affinity site for Mg(2). Biophys Chem. 209:28-40. doi: 10.1016/j.bpc.2015.10.009. [PubMed]

Luo M, Gates KS, Henzl MT, Tanner JJ. (2015). Diethylaminobenzaldehyde is a covalent, irreversible inactivator of ALDH7A1. ACS Chem Biol. 10(3):693-7. doi: 10.1021/cb500977q. [PubMed]

Henzl MT, Sirianni AG, Markus LA, Davis CM. (2015). Site-directed mutagenesis of rat α-parvalbumin: replacement of canonical CD-site residues with their non-consensus counterparts from rat β-parvalbumin. Biophys Chem. 197:25-39. doi: 10.1016/j.bpc.2014.12.002. [PubMed]