PDBsum entry 1itq

Hydrolase

PDB id: 1itq

Contents

Protein chains

369 a.a. *

Ligands

NAG ×4

Metals

_ZN ×4

Waters ×213

* Residue conservation analysis

PDB id:

1itq

Name:

Hydrolase

Title:

Human renal dipeptidase

Structure:

Renal dipeptidase. Chain: a, b. Synonym: microsomal dipeptidase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: renal cortex. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Biol. unit:

Dimer (from PQS)

Resolution:

2.30Å R-factor: 0.181 R-free: 0.258

Authors:

Y.Nitanai,Y.Satow,H.Adachi,M.Tsujimoto

Key ref:

Y.Nitanai et al. (2002). Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis. J Mol Biol, 321, 177-184. PubMed id: 12144777 DOI: 10.1016/S0022-2836(02)00632-0

Date:

02-Feb-02 Release date: 28-Aug-02

Protein chains

P16444  (DPEP1_HUMAN) -  Dipeptidase 1 from Homo sapiens

Seq: 411 a.a.

Struc: 369 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.4.13.19 - membrane dipeptidase.
• Reaction: an L-aminoacyl-L-amino acid + H2O = 2 an L-alpha-amino acid
• Cofactor: Zn(2+)
• Enzyme class 2: E.C.3.5.2.6 - beta-lactamase.

Pathway:

• Reaction: a beta-lactam + H2O = a substituted beta-amino acid
• Cofactor: Zn(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1016/S0022-2836(02)00632-0

J Mol Biol 321:177-184 (2002)

PubMed id: 12144777

Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis.

Y.Nitanai, Y.Satow, H.Adachi, M.Tsujimoto.

ABSTRACT

Human renal dipeptidase is a membrane-bound glycoprotein hydrolyzing dipeptides and is involved in hydrolytic metabolism of penem and carbapenem beta-lactam antibiotics. The crystal structures of the saccharide-trimmed enzyme are determined as unliganded and inhibitor-liganded forms. They are informative for designing new antibiotics that are not hydrolyzed by this enzyme. The active site in each of the (alpha/beta)(8) barrel subunits of the homodimeric molecule is composed of binuclear zinc ions bridged by the Glu125 side-chain located at the bottom of the barrel, and it faces toward the microvillar membrane of a kidney tubule. A dipeptidyl moiety of the therapeutically used cilastatin inhibitor is fully accommodated in the active-site pocket, which is small enough for precise recognition of dipeptide substrates. The barrel and active-site architectures utilizing catalytic metal ions exhibit unexpected similarities to those of the murine adenosine deaminase and the catalytic domain of the bacterial urease.

Selected figure(s)

Figure 1.
Figure 1. The overall view of the hrDP. (a) The dimeric structure of the hrDP viewed from the membrane-binding side. Ser369 anchored to the membrane is located on the C-terminal end, and the active sites are located on this side. The a-helices and the b-strands composing (a/b)[8] barrels are shown in green and yellow, respectively, and the a-helices capping the barrels are shown in magenta. Zinc ions are drawn as red spheres; cysteine residues forming disulfide bonds are drawn as yellow ball-and-sticks; N-linked N-acetylglucosamine molecules are drawn as pink ball-and-sticks. (b) The dimer viewed from a 90° rotation along the long axis of the dimer. (c) Stereo representation of a monomer subunit. (d) A drawing of the folding of the monomer subunit. The strands or helices are drawn to reflect their relative lengths. The color scheme and labels are consistent with those in (a) to (c). All Figures except Figure 2(a) and (c) were produced with MOLSCRIPT [30.] and Raster3D. [31.]

Figure 3.
Figure 3. Comparison of the architectures of the metallo-hydrolases having disordered (a/b)[8] barrels. (a) Arrangement of b-strands composing the barrels. Corresponding main-chain atoms of the b-strands are superimposed by least-squares fitting. The strands of subunit A of the hrDP are shown as yellow arrows; urease in sky-blue, phosphotriesterase in orange, and adenosine deaminase in red. The strands labeled b1 through b8 are sequentially arranged from the N-terminal side in each polypeptide. (b) Superimposition of the metal ions and ligands through least-squares fitting. The metal ions and ligand groups of the hrDP subunit A are drawn in yellow, urease in sky-blue, and phosphotriesterase in orange. Carbamoyllysine ligands are represented with Carb-K labels. The fittings in (a) and (b) were calculated independently.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 321, 177-184) copyright 2002.

Figures were selected by an automated process.