3VAT

Crystal structure of DNPEP, ZnMg form

Summary for 3VAT

• Entry DOI: 10.2210/pdb3vat/pdb
• Related: 3VAR
• Descriptor: Aspartyl aminopeptidase, ZINC ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: alpha-beta-alpha sandwich, aspartyl aminopeptidase, binuclear metal center, m18 peptidase, mh clan, tetrahedral aminopeptidase, hydrolase
• Biological source: Bos taurus (bovine)
• Cellular location: Cytoplasm: Q2HJH1
• Total number of polymer chains: 1
• Total formula weight: 55129.31

Authors

Kiser, P.D.,Chen, Y.,Palczewski, K. (deposition date: 2011-12-29, release date: 2012-02-29, Last modification date: 2023-09-13)

Primary citation

Chen, Y.,Farquhar, E.R.,Chance, M.R.,Palczewski, K.,Kiser, P.D.
Insights into substrate specificity and metal activation of Mammalian tetrahedral aspartyl aminopeptidase.
J.Biol.Chem., 287:13356-13370, 2012

PubMed Abstract: Aminopeptidases are key enzymes involved in the regulation of signaling peptide activity. Here, we present a detailed biochemical and structural analysis of an evolutionary highly conserved aspartyl aminopeptidase called DNPEP. We show that this peptidase can cleave multiple physiologically relevant substrates, including angiotensins, and thus may play a key role in regulating neuron function. Using a combination of x-ray crystallography, x-ray absorption spectroscopy, and single particle electron microscopy analysis, we provide the first detailed structural analysis of DNPEP. We show that this enzyme possesses a binuclear zinc-active site in which one of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity of the protein. The plasticity of this metal-binding site suggests a mechanism for regulation of DNPEP activity. We also demonstrate that DNPEP assembles into a functionally relevant tetrahedral complex that restricts access of peptide substrates to the active site. These structural data allow rationalization of the enzyme's preference for short peptide substrates with N-terminal acidic residues. This study provides a structural basis for understanding the physiology and bioinorganic chemistry of DNPEP and other M18 family aminopeptidases.

PubMed: 22356908
DOI: 10.1074/jbc.M112.347518

Experimental method

X-RAY DIFFRACTION (2.1 Å)