title: Crystal structure of the dinuclear zinc aminopeptidase PepV from Lactobacillus delbrueckii unravels its preference for dipeptides.
abstract: PepV from Lactobacillus delbrueckii, a dinuclear zinc peptidase, has been characterized as an unspecific amino dipeptidase. The crystal structure of PepV in complex with the phosphinic inhibitor AspPsi[PO(2)CH(2)]AlaOH, a dipeptide substrate mimetic, reveals a "catalytic domain" and a "lid domain," which together form an internal active site cavity that traps the inhibitor. The catalytic domain is topologically similar to catalytic domains from amino- and carboxypeptidases. However, the lid domain is unique among the related enzymes. In contrast to the other related exopeptidases, PepV recognizes and fixes the dipeptide backbone, while the side chains are not specifically probed and can vary, rendering it a nonspecific dipeptidase. The cocrystallized inhibitor illustrates the two roles of the two catalytic zinc ions, namely stabilization of the tetrahedral intermediate and activation of the catalytic water molecule.
authors.affiliation: Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, D-82152 Martinsried, Germany. jozic@biochem.mpg.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Jozic
authors.forename: Gleb
authors.initials: G
authors.lastname: Bourenkow
authors.forename: Hans
authors.initials: H
authors.lastname: Bartunik
authors.forename: Henning
authors.initials: H
authors.lastname: Scholze
authors.forename: Vincent
authors.initials: V
authors.lastname: Dive
authors.forename: Bernhard
authors.initials: B
authors.lastname: Henrich
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.forename: Wolfram
authors.initials: W
authors.lastname: Bode
authors.forename: Klaus
authors.initials: K
authors.lastname: Maskos
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000378:metabolism*; D007778:Lactobacillus / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D016415:Sequence Alignment; D015032:Zinc / Q000737:chemistry*; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004151:Dipeptides; D000626:Aminopeptidases; D011623:gamma-Glutamyl Hydrolase; D015032:Zinc