PDBsum entry 3ccc

Hydrolase

PDB id: 3ccc

Contents

Protein chain

724 a.a. *

Ligands

NAG-NAG ×4

NAG ×12

7AC ×4

Waters ×277

* Residue conservation analysis

PDB id:

3ccc

Name:

Hydrolase

Title:

Crystal structure of human dpp4 in complex with a benzimidazole derivative

Structure:

Dipeptidyl peptidase 4. Chain: a, b, c, d. Synonym: dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, adenosine deaminase complexing protein 2, adabp. Engineered: yes

Source:

Homo sapiens. Human. Gene: dpp4, adcp2, cd26. Expressed in: spodoptera frugiperda. Expression_system_cell_line: sf9.

Resolution:

2.71Å R-factor: 0.204 R-free: 0.267

Authors:

M.B.Wallace,R.J.Skene

Key ref:

M.B.Wallace et al. (2008). Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors. Bioorg Med Chem Lett, 18, 2362-2367. PubMed id: 18346892

Date:

25-Feb-08 Release date: 21-Oct-08

Protein chains

P27487  (DPP4_HUMAN) -  Dipeptidyl peptidase 4 from Homo sapiens

Seq: 766 a.a.

Struc: 724 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.

Bioorg Med Chem Lett 18:2362-2367 (2008)

PubMed id: 18346892

Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors.

M.B.Wallace, J.Feng, Z.Zhang, R.J.Skene, L.Shi, C.L.Caster, D.B.Kassel, R.Xu, S.L.Gwaltney.

ABSTRACT

A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been developed from a small fragment hit using structure-based drug design. A highly versatile synthetic route was created for the development of SAR, which led to the discovery of potent and selective inhibitors with excellent pharmaceutical properties.