PDBsum entry 6b7c

Transferase

PDB id: 6b7c

Contents

Protein chains

159 a.a.

Ligands

CWP ×2

SO4 ×4

PEG ×3

POP ×2

DMS ×3

Waters ×422

PDB id:

6b7c

Name:

Transferase

Title:

Crystal structure of e.Coli phosphopantetheine adenylyltransferase (ppat/coad) in complex with n-((1,3-dimethyl-1h-pyrazol-5-yl)methyl)- 5-methyl-1h-imidazo[4,5-b]pyridin-2-amine

Structure:

Phosphopantetheine adenylyltransferase. Chain: a, b. Synonym: dephospho-coa pyrophosphorylase,pantetheine-phosphate adenylyltransferase,ppat. Engineered: yes

Source:

Escherichia coli (strain k12). Organism_taxid: 83333. Strain: k12. Gene: coad, kdtb, yica, b3634, jw3609. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.56Å R-factor: 0.175 R-free: 0.199

Authors:

A.W.Proudfoot,D.Bussiere,A.Lingel

Key ref:

A.Proudfoot et al. (2017). High-Confidence Protein-Ligand Complex Modeling by NMR-Guided Docking Enables Early Hit Optimization. J Am Chem Soc, 139, 17824-17833. PubMed id: 29190085 DOI: 10.1021/jacs.7b07171

Date:

03-Oct-17 Release date: 27-Dec-17

Protein chains

P0A6I6  (COAD_ECOLI) -  Phosphopantetheine adenylyltransferase from Escherichia coli (strain K12)

Seq: 159 a.a.

Struc: 159 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.7.3 - pantetheine-phosphate adenylyltransferase.
• Pathway: Coenzyme A Biosynthesis (late stages)
• Reaction: (R)-4'-phosphopantetheine + ATP + H⁺ = 3'-dephospho-CoA + diphosphate

(R)-4'-phosphopantetheine + ATP + H(+) = 3'-dephospho-CoA + diphosphate (Bound ligand (Het Group name = POP) corresponds exactly)

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

Added reference

DOI no: 10.1021/jacs.7b07171

J Am Chem Soc 139:17824-17833 (2017)

PubMed id: 29190085

High-Confidence Protein-Ligand Complex Modeling by NMR-Guided Docking Enables Early Hit Optimization.

A.Proudfoot, D.E.Bussiere, A.Lingel.

ABSTRACT

Structure-based drug design is an integral part of modern day drug discovery and requires detailed structural characterization of protein-ligand interactions, which is most commonly performed by X-ray crystallography. However, the success rate of generating these costructures is often variable, in particular when working with dynamic proteins or weakly binding ligands. As a result, structural information is not routinely obtained in these scenarios, and ligand optimization is challenging or not pursued at all, representing a substantial limitation in chemical scaffolds and diversity. To overcome this impediment, we have developed a robust NMR restraint guided docking protocol to generate high-quality models of protein-ligand complexes. By combining the use of highly methyl-labeled protein with experimentally determined intermolecular distances, a comprehensive set of protein-ligand distances is generated which then drives the docking process and enables the determination of the correct ligand conformation in the bound state. For the first time, the utility and performance of such a method is fully demonstrated by employing the generated models for the successful, prospective optimization of crystallographically intractable fragment hits into more potent binders.