PDBsum entry 5inh

Hydrolase/hydrolase inhibitor

PDB id: 5inh

Contents

Protein chain

780 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN-MAN

NAG-NAG

NAG

ACT

6C1

Metals

_ZN ×2

_CA

Waters ×259

PDB id:

5inh

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of autotaxin/enpp2 with a covalent fragment

Structure:

Ectonucleotide pyrophosphatase/phosphodiesterase family member 2. Chain: a. Synonym: e-npp 2,autotaxin,extracellular lysophospholipase d,lysopld. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: enpp2, npps2, pdnp2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

1.84Å R-factor: 0.174 R-free: 0.207

Authors:

M.G.Klein,R.Tjhen

Key ref:

M.Lanier et al. (2017). Repurposing Suzuki Coupling Reagents as a Directed Fragment Library Targeting Serine Hydrolases and Related Enzymes. J Med Chem, 60, 5209-5215. PubMed id: 28564542

Date:

07-Mar-16 Release date: 15-Mar-17

Protein chain

Q9R1E6  (ENPP2_MOUSE) -  Autotaxin from Mus musculus

Seq: 862 a.a.

Struc: 780 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.1.4.39 - alkylglycerophosphoethanolamine phosphodiesterase.
• Reaction: a 1-O-alkyl-sn-glycero-3-phosphoethanolamine + H2O = a 1-O-alkyl- sn-glycero-3-phosphate + ethanolamine + H⁺

1-O-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-O-alkyl- sn-glycero-3-phosphate + ethanolamine (Bound ligand (Het Group name = ACT) matches with 60.00% similarity) + H(+)

• Enzyme class 2: E.C.3.1.4.4 - phospholipase D.
• Reaction: a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1,2-diacyl-sn-glycero- 3-phosphate + choline + H⁺

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

J Med Chem 60:5209-5215 (2017)

PubMed id: 28564542

Repurposing Suzuki Coupling Reagents as a Directed Fragment Library Targeting Serine Hydrolases and Related Enzymes.

M.Lanier, D.C.Cole, Y.Istratiy, M.G.Klein, P.A.Schwartz, R.Tjhen, A.Jennings, M.S.Hixon.

ABSTRACT

Serine hydrolases are susceptible to potent reversible inhibition by boronic acids. Large collections of chemically diverse boronic acid fragments are commercially available because of their utility in coupling chemistry. We repurposed the approximately 650 boronic acid reagents in our collection as a directed fragment library targeting serine hydrolases and related enzymes. Highly efficient hits (LE > 0.6) often result. The utility of the approach is illustrated with the results against autotaxin, a phospholipase implicated in cardiovascular disease.