PDBsum entry 4i7m

Hydrolase

PDB id: 4i7m

Contents

Protein chains

175 a.a.

Ligands

BME ×4

2LP ×2

SO4 ×6

HED

ACT ×2

Waters ×298

PDB id:

4i7m

Name:

Hydrolase

Title:

T4 lysozyme l99a/m102h with 2-allylphenol bound

Structure:

Lysozyme. Chain: a, b. Synonym: endolysin, lysis protein, muramidase. Engineered: yes. Mutation: yes

Source:

Enterobacteria phage t4. Organism_taxid: 10665. Gene: e. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.48Å R-factor: 0.175 R-free: 0.198

Authors:

M.Merski,B.K.Shoichet

Key ref:

M.Merski and B.K.Shoichet (2013). The impact of introducing a histidine into an apolar cavity site on docking and ligand recognition. J Med Chem, 56, 2874-2884. PubMed id: 23473072 DOI: 10.1021/jm301823g

Date:

30-Nov-12 Release date: 27-Mar-13

Protein chains

P00720  (ENLYS_BPT4) -  Endolysin from Enterobacteria phage T4

Seq: 164 a.a.

Struc: 175 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

DOI no: 10.1021/jm301823g

J Med Chem 56:2874-2884 (2013)

PubMed id: 23473072

The impact of introducing a histidine into an apolar cavity site on docking and ligand recognition.

M.Merski, B.K.Shoichet.

ABSTRACT

Simplified model binding sites allow one to isolate entangled terms in molecular energy functions. Here, we investigate the effects on ligand recognition of the introduction of a histidine into a hydrophobic cavity in lysozyme. We docked 656040 molecules and tested 26 highly and nine poorly ranked. Twenty-one highly ranked molecules bound and five were false positives, while three poorly ranked molecules were false negatives. In the 16 X-ray complexes now known, the docking predictions overlaid well with the crystallographic results. Although ligand enrichment was high, the false negatives, the false positives, and the inability to rank order illuminated weaknesses in our scoring, particularly overweighed apolar and underweighted polar terms. Adjusting these led to new problems, reflecting the entangled nature of docking scoring functions. Changes in ligand affinity relative to other lysozyme cavities speak to the subtleties of molecular recognition even in these simple sites and to their relevance for testing different models of recognition.