4AA7

E.coli GlmU in complex with an antibacterial inhibitor

Summary for 4AA7

• Entry DOI: 10.2210/pdb4aa7/pdb
• Related: 1FWY 1FXJ 1HV9
• Descriptor: BIFUNCTIONAL PROTEIN GLMU, N-(2,4-dimethoxy-5-{[(2R)-2-methyl-2,3-dihydro-1H-indol-1-yl]sulfonyl}phenyl)acetamide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: transferase, acetyl transferase, transferase-inhibitor complex
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 2
• Total formula weight: 50513.42

Authors

Otterbein, L.,Breed, J.,Ogg, D.J. (deposition date: 2011-11-30, release date: 2012-08-15, Last modification date: 2023-12-20)

Primary citation

Green, O.M.,McKenzie, A.R.,Shapiro, A.B.,Otterbein, L.,Ni, H.,Patten, A.,Stokes, S.,Albert, R.,Kawatkar, S.,Breed, J.
Inhibitors of Acetyltransferase Domain of N-Acetylglucosamine-1-Phosphate-Uridyltransferase/ Glucosamine-1-Phosphate-Acetyltransferase (Glmu). Part 1: Hit to Lead Evaluation of a Novel Arylsulfonamide Series.
Bioorg.Med.Chem.Lett., 22:1510-, 2012

PubMed Abstract: A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40.

PubMed: 22297115
DOI: 10.1016/J.BMCL.2012.01.016

Experimental method

X-RAY DIFFRACTION (2 Å)