4dyo

Crystal Structure of Human Aspartyl Aminopeptidase (DNPEP) in complex with Aspartic acid Hydroxamate

spinqualitylabelsall models 4dyo, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4dyo is a 1 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3l6s. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MG, SD4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DNPEP_HUMAN] Aminopeptidase with specificity towards an acidic amino acid at the N-terminus. Likely to play an important role in intracellular protein and peptide metabolism. Publication Abstract from PubMed ABSTRACT: Backround Aspartyl aminopeptidase (DNPEP), with specificity towards an acidic amino acid at the N-terminus, is the only mammalian member among the poorly understood M18 peptidases. DNPEP has implicated roles in protein and peptide metabolism, as well as the renin-angiotensin system in blood pressure regulation. Despite previous enzyme and substrate characterization, structural details of DNPEP regarding ligand recognition and catalytic mechanism remain to be delineated. RESULTS: The crystal structure of human DNPEP complexed with zinc and a substrate analogue aspartate-beta-hydroxamate reveals a dodecameric machinery built by domain-swapped dimers, in agreement with electron microscopy data. A structural comparison with bacterial homologues identifies unifying catalytic features among the poorly understood M18 enzymes. The bound ligands in the active site also reveal the coordination mode of the binuclear zinc centre and a substrate specificity pocket for acidic amino acids. CONCLUSIONS: The DNPEP structure provides a molecular framework to understand its catalysis that is mediated by active site loop swapping, a mechanism likely adopted in other M18 and M42 metallopeptidases that form dodecameric complexes as a self-compartmentalization strategy. Small differences in the substrate binding pocket such as shape and positive charges, the latter conferred by a basic lysine residue, further provide the key to distinguishing substrate preference. Together, the structural knowledge will aid in the development of enzyme-/family-specific aminopeptidase inhibitors. Structure of human aspartyl aminopeptidase complexed with substrate analogue: insight into catalytic mechanism, substrate specificity and M18 peptidase family.,Chaikuad A, Pilka ES, Riso AD, Delft FV, Kavanagh KL, Venien-Bryan C, Oppermann U, Yue WW BMC Struct Biol. 2012 Jun 21;12(1):14. PMID:22720794 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase 3D structures

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