PDBsum entry 5k1v

Hydrolase

PDB id: 5k1v

Contents

Protein chains

900 a.a.

849 a.a.

Ligands

NAG-NAG ×2

NAG-NAG-MAN-MAN

6PX

NAG ×12

Metals

_ZN ×2

Waters ×44

PDB id:

5k1v

Name:

Hydrolase

Title:

Crystal structure of endoplasmic reticulum aminopeptidase 2 (erap2) in complex with a diaminobenzoic acid derivative ligand.

Structure:

Endoplasmic reticulum aminopeptidase 2. Chain: a, b. Synonym: leukocyte-derived arginine aminopeptidase,l-rap. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: erap2, lrap. Expressed in: trichoplusia ni. Expression_system_taxid: 7111

Resolution:

2.90Å R-factor: 0.209 R-free: 0.273

Authors:

E.Saridakis,A.Papakyriakou,P.Giastas,A.Mpakali,I.M.Mavridis, E.Stratikos

Key ref:

A.Mpakali et al. (2017). Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency. Acs Med Chem Lett, 8, 333-337. PubMed id: 28337326

Date:

18-May-16 Release date: 29-Mar-17

Protein chain

Q6P179  (ERAP2_HUMAN) -  Endoplasmic reticulum aminopeptidase 2 from Homo sapiens

Seq: 960 a.a.

Struc: 900 a.a.

Protein chain

Q6P179  (ERAP2_HUMAN) -  Endoplasmic reticulum aminopeptidase 2 from Homo sapiens

Seq: 960 a.a.

Struc: 849 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.11.- - ?????

Acs Med Chem Lett 8:333-337 (2017)

PubMed id: 28337326

Crystal Structures of ERAP2 Complexed with Inhibitors Reveal Pharmacophore Requirements for Optimizing Inhibitor Potency.

A.Mpakali, P.Giastas, R.Deprez-Poulain, A.Papakyriakou, D.Koumantou, R.Gealageas, S.Tsoukalidou, D.Vourloumis, I.M.Mavridis, E.Stratikos, E.Saridakis.

ABSTRACT

Endoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses. To better understand the structural elements of inhibitors that govern their binding affinity to the ERAP2 active site, we cocrystallized ERAP2 with a medium activity 3,4-diaminobenzoic acid inhibitor and a poorly active hydroxamic acid derivative. Comparison of these two crystal structures with a previously solved structure of ERAP2 in complex with a potent phosphinic pseudopeptide inhibitor suggests that engaging the substrate N-terminus recognition properties of the active site is crucial for inhibitor binding even in the absence of a potent zinc-binding group. Proper utilization of all five major pharmacophores is necessary, however, to optimize inhibitor potency.