PDBsum entry 1v79

Hydrolase

PDB id: 1v79

Contents

Protein chain

349 a.a. *

Ligands

FR7

Metals

_ZN

Waters ×146

* Residue conservation analysis

PDB id:

1v79

Name:

Hydrolase

Title:

Crystal structures of adenosine deaminase complexed with potent inhibitors

Structure:

Adenosine deaminase. Chain: a. Synonym: adenosine aminohydrolase. Ec: 3.5.4.4

Source:

Bos taurus. Cattle. Organism_taxid: 9913

Resolution:

2.50Å R-factor: 0.256 R-free: 0.281

Authors:

T.Kinoshita

Key ref:

T.Terasaka et al. (2004). Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors. J Med Chem, 47, 2728-2731. PubMed id: 15139750 DOI: 10.1021/jm0499559

Date:

14-Dec-03 Release date: 21-Dec-04

Protein chain

P56658  (ADA_BOVIN) -  Adenosine deaminase from Bos taurus

Seq: 363 a.a.

Struc: 349 a.a.*

* PDB and UniProt seqs differ at 15 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.5.4.4 - adenosine deaminase.
• Reaction:
  1. adenosine + H2O + H⁺ = inosine + NH4⁺
  2. 2'-deoxyadenosine + H2O + H⁺ = 2'-deoxyinosine + NH4⁺

adenosine + H2O + H(+) = inosine (Bound ligand (Het Group name = FR7) matches with 46.43% similarity) + NH4(+)

2'-deoxyadenosine (Bound ligand (Het Group name = FR7) matches with 42.86% similarity) + H2O + H(+) = 2'-deoxyinosine + NH4(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/jm0499559

J Med Chem 47:2728-2731 (2004)

PubMed id: 15139750

Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.

T.Terasaka, H.Okumura, K.Tsuji, T.Kato, I.Nakanishi, T.Kinoshita, Y.Kato, M.Kuno, N.Seki, Y.Naoe, T.Inoue, K.Tanaka, K.Nakamura.

ABSTRACT

We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered two inhibitors with improved oral bioavailability [6 (K(i) = 13 nM, BA = 44%) and 7 (K(i) = 9.8 nM, BA = 42%)]. 6 demonstrated in vivo efficacy in models of inflammation and lymphoma.