Metal ion substitution in the catalytic site greatly affects the binding of sulfhydryl-containing compounds to leucyl aminopeptidase

Biochemistry
Mario CappielloUmberto Mura

Abstract

Bovine lens leucyl aminopeptidase (blLAP), a homohexameric metallopeptidase preferring bulky and hydrophobic amino acids at the N-terminus of (di)peptides, contains two Zn(2+) ions per subunit that are essential for catalytic activity. They may be replaced by other divalent cations with different exchange kinetics. The protein readily exchangeable site (site 1) can be occupied by Zn(2+), Mn(2+), Mg(2+), or Co(2+), while the tight binding site (site 2) can be occupied by Zn(2+) or Co(2+). We recently reported that introduction of Mn(2+) into site 1 generates a novel activity of blLAP toward CysGly [Cappiello, M., et al. (2004) Biochem. J. 378, 35-44], which in contrast is not hydrolyzed by the (Zn/Zn) enzyme. This finding, while disclosing a potential specific role for blLAP in glutathione metabolism, raised a question about the features required for molecules to be a substrate for the enzyme. To clarify the interaction of the enzyme with sulfhydryl-containing derivatives, (Zn/Zn)- and (Mn/Zn)blLAP forms were prepared and functional-structural studies were undertaken. Thus, a kinetic analysis of various compounds with both enzyme forms was performed; the crystal structure of (Zn/Zn)blLAP in complex with the peptidomimetic deriva...Continue Reading

References

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Oct 30, 2003·The Biochemical Journal·Mario CappielloUmberto Mura

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Citations

Dec 4, 2012·Analytical and Bioanalytical Chemistry·Mario CappielloUmberto Mura
Nov 30, 2006·Biological Chemistry·Mikiko MatsuiLinda L Walling
Apr 15, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Huong NgyenSiegmund Reissmann
Aug 20, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Mario CappielloAntonella Del-Corso
May 12, 2010·Biochimie·Artur MuchaPaweł Kafarski
Feb 5, 2011·Bioorganic & Medicinal Chemistry·Sébastien AlbrechtJean-Marc Weibel
Jan 17, 2020·Critical Reviews in Toxicology·Patrick E Hanna, M W Anders
Jun 29, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Jan PíchaArtur Mucha
Jul 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Henrique S FernandesNuno M F S A Cerqueira
May 26, 2017·Antioxidants & Redox Signaling·Anand Kumar Bachhawat, Amandeep Kaur
Sep 18, 2020·Journal of Medicinal Chemistry·Lukas RothRachel Codd

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