Structural highlights
1hm9 is a 2 chain structure with sequence from "diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , |
| Related: | 1hm8, 1hm0, 1fxj, 1fwy |
| Gene: | GLMU ("Diplococcus pneumoniae" (Klein 1884) Weichselbaum 1886) |
| Activity: | UDP-N-acetylglucosamine diphosphorylase, with EC number 2.7.7.23 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GLMU_STRPN] 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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of Streptococcus pneumoniae N-acetylglucosamine-1-phosphate uridyltransferase bound to acetyl-coenzyme A reveals a novel active site architecture.,Sulzenbacher G, Gal L, Peneff C, Fassy F, Bourne Y J Biol Chem. 2001 Apr 13;276(15):11844-51. Epub 2000 Dec 15. PMID:11118459[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. 2001 Apr 13;276(15):11844-51. Epub 2000 Dec 15. PMID:11118459 doi:10.1074/jbc.M011225200
