PDBsum entry: 1w1i

Hydrolase

PDB id: 1w1i

Contents

Protein chains

728 a.a. *

352 a.a. *

Ligands

NAG-NAG-FUC ×2

NAG-NAG ×9

NAG-NAG-BMA-MAN ×4

NAG ×12

NDG ×3

NAG-FUC ×2

Metals

_ZN ×4

* Residue conservation analysis

PDB id:

1w1i

Name:

Hydrolase

Title:

Crystal structure of dipeptidyl peptidase iv (dppiv or cd26) in complex with adenosine deaminase

Structure:

Dipeptidyl peptidase iv. Chain: a, b, c, d. Fragment: extracellular domain 39 - 766. Synonym: dpp iv, t-cell activation antigen cd26, tp103, adenosine deaminase complexing protein-2, adabp. Engineered: yes. Adenosine deaminase. Chain: e, f, g, h. Synonym: adenosine aminohydrolase.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: kidney. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Bos taurus. Bovine. Organism_taxid: 9913.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.03Å R-factor: 0.224 R-free: 0.257

Authors:

W.A.Weihofen,J.Liu,W.Reutter,W.Saenger,H.Fan

Key ref:

W.A.Weihofen et al. (2004). Crystal structure of CD26/dipeptidyl-peptidase IV in complex with adenosine deaminase reveals a highly amphiphilic interface. J Biol Chem, 279, 43330-43335. PubMed id: 15213224 DOI: 10.1074/jbc.M405001200

Date:

22-Jun-04 Release date: 02-Sep-04

Protein chains

P27487  (DPP4_HUMAN) -  Dipeptidyl peptidase 4

Seq: 766 a.a.

Struc: 728 a.a.

Protein chains

P56658  (ADA_BOVIN) -  Adenosine deaminase

Seq: 363 a.a.

Struc: 352 a.a.*

* PDB and UniProt seqs differ at 16 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chains A, B, C, D: E.C.3.4.14.5 - Dipeptidyl-peptidase Iv.
• Reaction: Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, from a polypeptide, preferentially when Xbb is Pro, provided Xcc is neither Pro nor hydroxyproline.
• Enzyme class 2: Chains E, F, G, H: E.C.3.5.4.4 - Adenosine deaminase.
• Reaction: Adenosine + H₂O = inosine + NH₃

Adenosine (Bound ligand (Het Group name = NAG) matches with 57.00% similarity) + H(2)O = inosine + NH(3)

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

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (24 terms)
• Biological process: establishment of localization (49 terms)
• Biochemical function: protein binding (17 terms)

Added reference

DOI no: 10.1074/jbc.M405001200

J Biol Chem 279:43330-43335 (2004)

PubMed id: 15213224

Crystal structure of CD26/dipeptidyl-peptidase IV in complex with adenosine deaminase reveals a highly amphiphilic interface.

W.A.Weihofen, J.Liu, W.Reutter, W.Saenger, H.Fan.

ABSTRACT

Dipeptidyl-peptidase IV (DPPIV or CD26) is a homodimeric type II membrane glycoprotein in which the two monomers are subdivided into a beta-propeller domain and an alpha/beta-hydrolase domain. As dipeptidase, DPPIV modulates the activity of various biologically important peptides and, in addition, DPPIV acts as a receptor for adenosine deaminase (ADA), thereby mediating co-stimulatory signals in T-lymphocytes. The 3.0-A resolution crystal structure of the complex formed between human DPPIV and bovine ADA presented here shows that each beta-propeller domain of the DPPIV dimer binds one ADA. At the binding interface, two hydrophobic loops protruding from the beta-propeller domain of DPPIV interact with two hydrophilic and heavily charged alpha-helices of ADA, giving rise to the highest percentage of charged residues involved in a protein-protein contact reported thus far. Additionally, four glycosides linked to Asn229 of DPPIV bind to ADA. In the crystal structure of porcine DPPIV, the observed tetramer formation was suggested to mediate epithelial and lymphocyte cell-cell adhesion. ADA binding to DPPIV could regulate this adhesion, as it would abolish tetramerization.

Selected figure(s)

Figure 2.
FIG. 2. Glycoside residues bound to Asn229 of hDPPIV interact with 33Arg-Arg-Gly-Ile^36 of bADA. Electron density is drawn at the 1.2 level. Carbon atoms are gray, oxygen is red, and nitrogen is blue. The dashed black line indicates a hydrogen bond (Man[3]O2H:Gly35O, 2.6 Å). MAN, mannose; NAG, N-acetylglucosamine.

Figure 4.
FIG. 4. The interface between bADA and hDPPIV. A, stereo plot of the hDPPIV·bADA interface, with bADA segments in green and hDPPIV segments in gray. Hydrogen bonds are indicated by black dashed lines. B, schematic representation of interactions between hDPPIV and bADA residues. Carbon atoms are shown in black, and nitrogen and oxygen atoms are as described in the legend to Fig. 2. Distances are in Å. Direct hydrogen bonds between proteins are shown as green dashed lines, and hydrophobic contacts are indicated by red eyelashes. This figure was partly generated with Ligplot (34).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 43330-43335) copyright 2004.

Figures were selected by the author.