PDBsum entry 3iqh

Transferase

PDB id: 3iqh

Contents

Protein chain

310 a.a. *

Ligands

TYR-ASP-ILE

SO4

Waters ×236

* Residue conservation analysis

PDB id:

3iqh

Name:

Transferase

Title:

Structure of o-acetylserine sulfhydrylase in complex with peptide mnydi

Structure:

Cysteine synthase. Chain: x. Synonym: csase, o-acetylserine sulfhydrylase, o-acetylserine (thiol)- lyase, oas-tl. Engineered: yes. Mnydi. Chain: p. Engineered: yes

Source:

Haemophilus influenzae. Organism_taxid: 727. Gene: cysk, hi1103. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Resolution:

1.90Å R-factor: 0.165 R-free: 0.209

Authors:

S.L.Roderick

Key ref:

E.Salsi et al. (2010). Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature. J Med Chem, 53, 345-356. PubMed id: 19928859

Date:

20-Aug-09 Release date: 17-Nov-09

Protein chain

P45040  (CYSK_HAEIN) -  Cysteine synthase from Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Seq: 316 a.a.

Struc: 310 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.5.1.47 - cysteine synthase.
• Reaction: O-acetyl-L-serine + hydrogen sulfide = L-cysteine + acetate

O-acetyl-L-serine + hydrogen sulfide = L-cysteine (Bound ligand (Het Group name = ASP) matches with 50.00% similarity) + acetate (Bound ligand (Het Group name = ILE) matches with 60.00% similarity)

• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = TYR) matches with 40.00% similarity)

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

reference

J Med Chem 53:345-356 (2010)

PubMed id: 19928859

Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature.

E.Salsi, A.S.Bayden, F.Spyrakis, A.Amadasi, B.Campanini, S.Bettati, T.Dodatko, P.Cozzini, G.E.Kellogg, P.F.Cook, S.L.Roderick, A.Mozzarelli.

ABSTRACT

The inhibition of cysteine biosynthesis in prokaryotes and protozoa has been proposed to be relevant for the development of antibiotics. Haemophilus influenzae O-acetylserine sulfhydrylase (OASS), catalyzing l-cysteine formation, is inhibited by the insertion of the C-terminal pentapeptide (MNLNI) of serine acetyltransferase into the active site. Four-hundred MNXXI pentapeptides were generated in silico, docked into OASS active site using GOLD, and scored with HINT. The terminal P5 Ile accounts for about 50% of the binding energy. Glu or Asp at position P4 and, to a lesser extent, at position P3 also significantly contribute to the binding interaction. The predicted affinity of 14 selected pentapeptides correlated well with the experimentally determined dissociation constants. The X-ray structure of three high affinity pentapeptide-OASS complexes were compared with the docked poses. These results, combined with a GRID analysis of the active site, allowed us to define a pharmacophoric scaffold for the design of peptidomimetic inhibitors.