PDBsum entry 3d4l

Hydrolase

PDB id: 3d4l

Contents

Protein chain

728 a.a. *

Ligands

NAG-NDG ×2

NAG-NAG ×7

NAG ×6

605 ×2

Metals

_NA

Waters ×982

* Residue conservation analysis

PDB id:

3d4l

Name:

Hydrolase

Title:

Human dipeptidyl peptidase iv/cd26 in complex with a novel inhibitor

Structure:

Dipeptidyl peptidase 4 soluble form. Chain: a, b. Fragment: extracellular domain (residues 39-766). Synonym: dipeptidyl peptidase iv, dpp iv, t-cell activation antigen cd26, tp103, adenosine deaminase complexing protein 2, adabp, 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.

Resolution:

2.00Å R-factor: 0.220 R-free: 0.217

Authors:

G.Scapin

Key ref:

G.B.Liang et al. (2008). Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design. Bioorg Med Chem Lett, 18, 3706-3710. PubMed id: 18524582

Date:

14-May-08 Release date: 01-Jul-08

Protein chains

P27487  (DPP4_HUMAN) -  Dipeptidyl peptidase 4 from Homo sapiens

Seq: 766 a.a.

Struc: 728 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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 18:3706-3710 (2008)

PubMed id: 18524582

Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design.

G.B.Liang, X.Qian, T.Biftu, S.Singh, Y.D.Gao, G.Scapin, S.Patel, B.Leiting, R.Patel, J.Wu, X.Zhang, N.A.Thornberry, A.E.Weber.

ABSTRACT

Probing with tool molecules, and by modeling and X-ray crystallography the binding modes of two structurally distinct series of DPP-4 inhibitors led to the discovery of a rare aromatic fluorine H-bond and the spatial requirement for better biaryl binding in the DPP-4 enzyme active site. These newly found binding elements were successfully incorporated into novel DPP-4 inhibitors.