PDBsum entry 5b5t

Hydrolase/hydrolase inhibitor

PDB id: 5b5t

Contents

Protein chains

349 a.a.

190 a.a.

Ligands

6FY ×2

Metals

_CA ×2

Waters ×1274

PDB id:

5b5t

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of escherichia coli gamma-glutamyltranspeptidase in complex with peptidyl phosphonate inhibitor 1b

Structure:

Gamma-glutamyltranspeptidase large chain. Chain: a, c. Synonym: glutathione hydrolase, gamma-glutamyltranspeptidase large- subunit. Engineered: yes. Gamma-glutamyltranspeptidase small chain. Chain: b, d. Synonym: glutathione hydrolase, gamma-glutamyltranspeptidase small- subunit.

Source:

Escherichia coli (strain k12). Organism_taxid: 83333. Strain: k12. Gene: ggt, b3447, jw3412. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.70Å R-factor: 0.179 R-free: 0.194

Authors:

K.Wada,K.Fukuyama

Key ref:

A.Kamiyama et al. (2016). Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity. Bioorg Med Chem Lett, 24, 5340-5352. PubMed id: 27622749 DOI: 10.1016/j.bmc.2016.08.050

Date:

18-May-16 Release date: 28-Sep-16

Protein chains

P18956  (GGT_ECOLI) -  Glutathione hydrolase proenzyme from Escherichia coli (strain K12)

Seq: 580 a.a.

Struc: 349 a.a.

Protein chains

P18956  (GGT_ECOLI) -  Glutathione hydrolase proenzyme from Escherichia coli (strain K12)

Seq: 580 a.a.

Struc: 190 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D: E.C.2.3.2.2 - gamma-glutamyltransferase.
• Reaction: an N-terminal (5-L-glutamyl)-[peptide] + an alpha-amino acid = 5-L- glutamyl amino acid + an N-terminal L-alpha-aminoacyl-[peptide]

N-terminal (5-L-glutamyl)-[peptide] + alpha-amino acid = 5-L- glutamyl amino acid (Bound ligand (Het Group name = 6FY) matches with 40.00% similarity) + N-terminal L-alpha-aminoacyl-[peptide]

• Enzyme class 3: Chains A, B, C, D: E.C.3.4.19.13 - glutathione gamma-glutamate hydrolase.
• Reaction:
  1. glutathione + H2O = L-cysteinylglycine + L-glutamate
  2. an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamate

glutathione + H2O = L-cysteinylglycine (Bound ligand (Het Group name = 6FY) matches with 40.91% similarity) + L-glutamate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.bmc.2016.08.050

Bioorg Med Chem Lett 24:5340-5352 (2016)

PubMed id: 27622749

Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity.

A.Kamiyama, M.Nakajima, L.Han, K.Wada, M.Mizutani, Y.Tabuchi, A.Kojima-Yuasa, I.Matsui-Yuasa, H.Suzuki, K.Fukuyama, B.Watanabe, J.Hiratake.

ABSTRACT

No abstract given.