1HM8

CRYSTAL STRUCTURE OF S.PNEUMONIAE N-ACETYLGLUCOSAMINE-1-PHOSPHATE URIDYLTRANSFERASE, GLMU, BOUND TO ACETYL COENZYME A

Summary for 1HM8

• Entry DOI: 10.2210/pdb1hm8/pdb
• Related: 1FWY 1FXJ 1HM0 1HM9
• Descriptor: UDP-N-ACETYLGLUCOSAMINE-1-PHOSPHATE URIDYLTRANSFERASE, CALCIUM ION, ACETYL COENZYME *A, ... (4 entities in total)
• Functional Keywords: acetyltransferase, bifunctional, drug design, pyrophosphorylase rossmann-like fold, left-handed-beta-helix, trimer, domain-interchange, transferase
• Biological source: Streptococcus pneumoniae
• Cellular location: Cytoplasm: Q97R46
• Total number of polymer chains: 2
• Total formula weight: 102858.66

Authors

Sulzenbacher, G.,Gal, L.,Peneff, C.,Fassy, F.,Bourne, Y. (deposition date: 2000-12-05, release date: 2001-11-30, Last modification date: 2024-02-07)

Primary citation

Sulzenbacher, G.,Gal, L.,Peneff, C.,Fassy, F.,Bourne, Y.
Crystal structure of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyltransferase bound to acetyl-coenzyme A reveals a novel active site architecture.
J.Biol.Chem., 276:11844-11851, 2001

PubMed Abstract: The bifunctional bacterial enzyme N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the two-step formation of UDP-GlcNAc, a fundamental precursor in bacterial cell wall biosynthesis. With the emergence of new resistance mechanisms against beta-lactam and glycopeptide antibiotics, the biosynthetic pathway of UDP-GlcNAc represents an attractive target for drug design of new antibacterial agents. The crystal structures of Streptococcus pneumoniae GlmU in unbound form, in complex with acetyl-coenzyme A (AcCoA) and in complex with both AcCoA and the end product UDP-GlcNAc, have been determined and refined to 2.3, 2.5, and 1.75 A, respectively. The S. pneumoniae GlmU molecule is organized in two separate domains connected via a long alpha-helical linker and associates as a trimer, with the 50-A-long left-handed beta-helix (LbetaH) C-terminal domains packed against each other in a parallel fashion and the C-terminal region extended far away from the LbetaH core and exchanged with the beta-helix from a neighboring subunit in the trimer. AcCoA binding induces the formation of a long and narrow tunnel, enclosed between two adjacent LbetaH domains and the interchanged C-terminal region of the third subunit, giving rise to an original active site architecture at the junction of three subunits.

PubMed: 11118459
DOI: 10.1074/jbc.M011225200

Experimental method

X-RAY DIFFRACTION (2.5 Å)