PDBsum entry 4cdc

Hydrolase

PDB id: 4cdc

Contents

Protein chains

114 a.a.

162 a.a.

68 a.a.

Ligands

NAG ×7

6AO ×4

GOL ×4

Metals

_CL ×4

Waters ×311

PDB id:

4cdc

Name:

Hydrolase

Title:

Human dpp1 in complex with (2s)-2-amino-n-((1s)-1-cyano-2-(4- phenylphenyl)ethyl)butanamide

Structure:

Dipeptidyl peptidase 1 exclusion domain chain. Chain: a, d, g, j. Fragment: dpp1 exclusion domain, residues 25-143. Synonym: dipeptidyl peptidase i exclusion domain chain, cathepsin c, cathepsin j, dipeptidyl peptidase i, dpp-i, dppi, dipeptidyl transferase. Engineered: yes. Dipeptidyl peptidase 1 heavy chain. Chain: b, e, h, k.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.

Resolution:

2.40Å R-factor: 0.193 R-free: 0.233

Authors:

J.Debreczeni,K.Edman,M.Furber,A.Tiden,P.Gardiner,T.Mete,R.Ford, I.Millichip,L.Stein,A.Mather,E.Kinchin,C.Luckhurst,P.Cage, H.Sanghanee,J.Breed,L.Wissler

Key ref:

M.Furber et al. (2014). Cathepsin C inhibitors: property optimization and identification of a clinical candidate. J Med Chem, 57, 2357-2367. PubMed id: 24592859 DOI: 10.1021/jm401705g

Date:

31-Oct-13 Release date: 19-Mar-14

Protein chains

P53634  (CATC_HUMAN) -  Dipeptidyl peptidase 1 from Homo sapiens

Seq: 463 a.a.

Struc: 114 a.a.

Protein chains

P53634  (CATC_HUMAN) -  Dipeptidyl peptidase 1 from Homo sapiens

Seq: 463 a.a.

Struc: 162 a.a.

Protein chains

P53634  (CATC_HUMAN) -  Dipeptidyl peptidase 1 from Homo sapiens

Seq: 463 a.a.

Struc: 68 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H, I, J, K, L: E.C.3.4.14.1 - dipeptidyl-peptidase I.
• Reaction: Release of an N-terminal dipeptide, Xaa-Xbb-|-Xcc, except when Xaa is Arg or Lys, or Xbb or Xcc is Pro.

DOI no: 10.1021/jm401705g

J Med Chem 57:2357-2367 (2014)

PubMed id: 24592859

Cathepsin C inhibitors: property optimization and identification of a clinical candidate.

M.Furber, A.K.Tiden, P.Gardiner, A.Mete, R.Ford, I.Millichip, L.Stein, A.Mather, E.Kinchin, C.Luckhurst, S.Barber, P.Cage, H.Sanganee, R.Austin, K.Chohan, R.Beri, B.Thong, A.Wallace, V.Oreffo, R.Hutchinson, S.Harper, J.Debreczeni, J.Breed, L.Wissler, K.Edman.

ABSTRACT

A lead generation and optimization program delivered the highly selective and potent CatC inhibitor 10 as an in vivo tool compound and potential development candidate. Structural studies were undertaken to generate SAR understanding.