2ewb
From Proteopedia
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'''The crystal structure of Bovine Lens Leucine Aminopeptidase in complex with zofenoprilat''' | '''The crystal structure of Bovine Lens Leucine Aminopeptidase in complex with zofenoprilat''' | ||
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[[Category: Pedone, C.]] | [[Category: Pedone, C.]] | ||
[[Category: Simone, G De.]] | [[Category: Simone, G De.]] | ||
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| - | [[Category: | + | [[Category: Metallopeptidase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:11:19 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 00:11, 4 May 2008
The crystal structure of Bovine Lens Leucine Aminopeptidase in complex with zofenoprilat
Overview
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 derivative Zofenoprilat was determined, and a modeling study on the CysGly-(Zn/Zn)blLAP complex was carried out. This combined approach provided insight into the interaction of blLAP with sulfhydryl-containing derivatives, showing that the metal exchange in site 1 modulates binding to these molecules that may result in enzyme substrates or inhibitors, depending on the nature of the metal.
About this Structure
2EWB is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
Reference
Metal ion substitution in the catalytic site greatly affects the binding of sulfhydryl-containing compounds to leucyl aminopeptidase., Cappiello M, Alterio V, Amodeo P, Del Corso A, Scaloni A, Pedone C, Moschini R, De Donatis GM, De Simone G, Mura U, Biochemistry. 2006 Mar 14;45(10):3226-34. PMID:16519517 Page seeded by OCA on Sun May 4 03:11:19 2008
