Structural highlights
Function
[GLMU_STRR6] Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain (By similarity).
Publication Abstract from PubMed
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-acetylt ransferase (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.
Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetylt ransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series.,Green OM, McKenzie AR, Shapiro AB, Otterbein L, Ni H, Patten A, Stokes S, Albert R, Kawatkar S, Breed J Bioorg Med Chem Lett. 2012 Feb 15;22(4):1510-9. Epub 2012 Jan 14. PMID:22297115[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Green OM, McKenzie AR, Shapiro AB, 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-acetylt ransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1510-9. Epub 2012 Jan 14. PMID:22297115 doi:10.1016/j.bmcl.2012.01.016
