PDBsum entry 3w2t

Hydrolase/hydrolase inhibitor

PDB id: 3w2t

Contents

Protein chain

729 a.a.

Ligands

NAG-FUL ×2

NAG-NAG ×6

LF7 ×2

GOL ×2

NAG ×5

Waters ×1027

PDB id:

3w2t

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of human depiptidyl peptidase iv (dpp-4) in complex with vildagliptin

Structure:

Dipeptidyl peptidase 4. Chain: a, b. Fragment: unp residues 33-766. Synonym: adabp, adenosine deaminase complexing protein 2, adcp-2, dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, dipeptidyl peptidase 4 membrane form, dipeptidyl peptidase iv membrane form, dipeptidyl peptidase 4 soluble form, dipeptidyl peptidase iv soluble form. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dpp4, adcp2, cd26. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: expressf+.

Resolution:

2.36Å R-factor: 0.183 R-free: 0.231

Authors:

H.Kishida,M.Nabeno,I.Miyaguchi,Y.Tanaka,R.Katou,F.Akahoshi

Key ref:

M.Nabeno et al. (2013). A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochem Biophys Res Commun, 434, 191-196. PubMed id: 23501107 DOI: 10.1016/j.bbrc.2013.03.010

Date:

04-Dec-12 Release date: 15-May-13

Protein chains

P27487  (DPP4_HUMAN) -  Dipeptidyl peptidase 4 from Homo sapiens

Seq: 766 a.a.

Struc: 729 a.a.

Enzyme reactions

• Enzyme class: 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.

DOI no: 10.1016/j.bbrc.2013.03.010

Biochem Biophys Res Commun 434:191-196 (2013)

PubMed id: 23501107

A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site.

M.Nabeno, F.Akahoshi, H.Kishida, I.Miyaguchi, Y.Tanaka, S.Ishii, T.Kadowaki.

ABSTRACT

In recent years, various dipeptidyl peptidase IV (DPP-4) inhibitors have been released as therapeutic drugs for type 2 diabetes in many countries. In spite of their diverse chemical structures, no comparative studies of their binding modes in the active site of DPP-4 have been disclosed. We determined the co-crystal structure of vildagliptin with DPP-4 by X-ray crystallography and compared the binding modes of six launched inhibitors in DPP-4. The inhibitors were categorized into three classes on the basis of their binding subsites: (i) vildagliptin and saxagliptin (Class 1) form interactions with the core S1 and S2 subsites and a covalent bond with Ser630 in the catalytic triad; (ii) alogliptin and linagliptin (Class 2) form interactions with the S1' and/or S2' subsites in addition to the S1 and S2 subsites; and (iii) sitagliptin and teneligliptin (Class 3) form interactions with the S1, S2 and S2 extensive subsites. The present study revealed that the additional interactions with the S1', S2' or S2 extensive subsite may increase DPP-4 inhibition beyond the level afforded by the fundamental interactions with the S1 and S2 subsites and are more effective than forming a covalent bond with Ser630.