PDBsum entry 4l72

Hydrolase/viral protein

PDB id: 4l72

Contents

Protein chains

728 a.a.

204 a.a.

Ligands

NAG-NAG ×2

NAG-NAG-BMA

NAG ×5

PDB id:

4l72

Name:

Hydrolase/viral protein

Title:

Crystal structure of mers-cov complexed with human dpp4

Structure:

Dipeptidyl peptidase 4. Chain: a. Fragment: unp residues 39-766. 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. Middle east respiratory syndrome coronavirus. Mers-cov. Organism_taxid: 1335626.

Resolution:

3.01Å R-factor: 0.208 R-free: 0.253

Authors:

X.Q.Wang,N.S.Wang

Key ref:

N.Wang et al. (2013). Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res, 23, 986-993. PubMed id: 23835475 DOI: 10.1038/cr.2013.92

Date:

13-Jun-13 Release date: 21-Aug-13

Protein chain

P27487  (DPP4_HUMAN) -  Dipeptidyl peptidase 4 from Homo sapiens

Seq: 766 a.a.

Struc: 728 a.a.

Protein chain

R9UQ53  (R9UQ53_MERS) -  Spike glycoprotein from Middle East respiratory syndrome-related coronavirus

Seq: 1353 a.a.

Struc: 204 a.a.

Enzyme reactions

• Enzyme class: Chain A: 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: 10.1038/cr.2013.92

Cell Res 23:986-993 (2013)

PubMed id: 23835475

Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4.

N.Wang, X.Shi, L.Jiang, S.Zhang, D.Wang, P.Tong, D.Guo, L.Fu, Y.Cui, X.Liu, K.C.Arledge, Y.H.Chen, L.Zhang, X.Wang.

ABSTRACT

The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 Å-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 β-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.