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PDBsum entry 1itq

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
1itq
Jmol
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P16444  (DPEP1_HUMAN) -  Dipeptidase 1
Seq:
Struc:
411 a.a.
369 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.4.13.19  - Membrane dipeptidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of dipeptides. Hydrophobic dipeptides are cleaved preferentially, including prolyl amino acids.
      Cofactor: Zn(2+)
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   9 terms 
  Biological process     cellular response to drug   14 terms 
  Biochemical function     modified amino acid binding     13 terms  

 

 
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20000809 J.A.Cummings, T.T.Nguyen, A.A.Fedorov, P.Kolb, C.Xu, E.V.Fedorov, B.K.Shoichet, D.P.Barondeau, S.C.Almo, and F.M.Raushel (2010).
Structure, mechanism, and substrate profile for Sco3058: the closest bacterial homologue to human renal dipeptidase .
  Biochemistry, 49, 611-622.
PDB codes: 3id7 3itc 3k5x
18931951 R.O'Dwyer, R.Razzaque, X.Hu, S.K.Hollingshead, and J.G.Wall (2009).
Engineering of cysteine residues leads to improved production of a human dipeptidase enzyme in E. coli.
  Appl Biochem Biotechnol, 159, 178-190.  
17397529 E.Ristoff, and A.Larsson (2007).
Inborn errors in the metabolism of glutathione.
  Orphanet J Rare Dis, 2, 16.  
17567047 R.S.Hall, D.F.Xiang, C.Xu, and F.M.Raushel (2007).
N-Acetyl-D-glucosamine-6-phosphate deacetylase: substrate activation via a single divalent metal ion.
  Biochemistry, 46, 7942-7952.  
16963440 M.Goto, H.Hayashi, I.Miyahara, K.Hirotsu, M.Yoshida, and T.Oikawa (2006).
Crystal structures of nonoxidative zinc-dependent 2,6-dihydroxybenzoate (gamma-resorcylate) decarboxylase from Rhizobium sp. strain MTP-10005.
  J Biol Chem, 281, 34365-34373.
PDB codes: 2dvt 2dvu 2dvx
15006780 D.H.Baek, J.J.Song, S.J.Kwon, C.Park, C.M.Jung, and M.H.Sung (2004).
Characteristics of a new enantioselective thermostable dipeptidase from Brevibacillus borstelensis BCS-1 and its application to synthesis of a D-amino-acid-containing dipeptide.
  Appl Environ Microbiol, 70, 1570-1575.  
14557261 F.Vincent, D.Yates, E.Garman, G.J.Davies, and J.A.Brannigan (2004).
The three-dimensional structure of the N-acetylglucosamine-6-phosphate deacetylase, NagA, from Bacillus subtilis: a member of the urease superfamily.
  J Biol Chem, 279, 2809-2816.
PDB codes: 1un7 2vhl
15044722 M.Bochtler, S.G.Odintsov, M.Marcyjaniak, and I.Sabala (2004).
Similar active sites in lysostaphins and D-Ala-D-Ala metallopeptidases.
  Protein Sci, 13, 854-861.  
14736882 W.L.Lai, L.Y.Chou, C.Y.Ting, R.Kirby, Y.C.Tsai, A.H.Wang, and S.H.Liaw (2004).
The functional role of the binuclear metal center in D-aminoacylase: one-metal activation and second-metal attenuation.
  J Biol Chem, 279, 13962-13967.
PDB codes: 1rjp 1rjq 1rjr 1rk5 1rk6 1v4y 1v51
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.