Bifunctional protein GlmU

Details

Name
Bifunctional protein GlmU
Kind
protein
Synonyms
  • 2.7.7.23
Gene Name
glmU
UniProtKB Entry
P43889Swiss-Prot
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
NCBI Taxonomy ID
71421
Amino acid sequence
>lcl|BSEQ0012983|Bifunctional protein GlmU
MTKKALSAVILAAGKGTRMYSDLPKVLHTIAGKPMVKHVIDTAHQLGSENIHLIYGHGGD
LMRTHLANEQVNWVLQTEQLGTAHAVQQAAPFFKDNENIVVLYGDAPLITKETLEKLIEA
KPENGIALLTVNLDNPTGYGRIIRENGNVVAIVEQKDANAEQLNIKEVNTGVMVSDGASF
KKWLARVGNNNAQGEYYLTDLIALANQDNCQVVAVQATDVMEVEGANNRLQLAALERYFQ
NKQASKLLLEGVMIYDPARFDLRGTLEHGKDVEIDVNVIIEGNVKLGDRVKIGTGCVLKN
VVIGNDVEIKPYSVLEDSIVGEKAAIGPFSRLRPGAELAAETHVGNFVEIKKSTVGKGSK
VNHLTYVGDSEIGSNCNIGAGVITCNYDGANKFKTIIGDDVFVGSDTQLVAPVKVANGAT
IGAGTTITRDVGENELVITRVAQRHIQGWQRPIKKK
Number of residues
456
Molecular Weight
49287.025
Theoretical pI
6.59
GO Classification
Functions
glucosamine-1-phosphate N-acetyltransferase activity / magnesium ion binding / UDP-N-acetylglucosamine diphosphorylase activity
Processes
cell morphogenesis / cell wall organization / lipid A biosynthetic process / lipopolysaccharide biosynthetic process / peptidoglycan biosynthetic process / regulation of cell shape / UDP-N-acetylglucosamine biosynthetic process
Components
cytoplasm
General Function
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.
Specific Function
glucosamine-1-phosphate N-acetyltransferase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0012984|Bifunctional protein GlmU (glmU)
ATGACAAAAAAAGCATTAAGTGCGGTAATTTTAGCAGCTGGAAAAGGAACGCGTATGTAT
TCTGATTTACCCAAAGTTCTACATACAATCGCGGGTAAACCAATGGTAAAACACGTGATT
GATACTGCCCATCAATTAGGCTCAGAAAATATTCATTTAATCTATGGTCACGGTGGGGAC
TTAATGCGTACCCATCTTGCGAATGAACAAGTAAATTGGGTATTACAAACAGAACAACTT
GGCACAGCACATGCAGTTCAACAAGCAGCACCTTTCTTTAAAGATAACGAAAACATTGTT
GTGCTTTACGGCGATGCACCATTAATTACTAAAGAAACATTAGAAAAATTAATTGAAGCG
AAACCAGAAAATGGCATTGCATTGCTTACCGTAAATTTAGATAACCCAACAGGCTATGGA
CGAATTATCCGTGAAAATGGGAACGTTGTAGCCATTGTAGAACAAAAAGATGCGAATGCT
GAGCAACTAAATATTAAAGAAGTCAATACTGGCGTTATGGTATCTGATGGTGCAAGTTTC
AAAAAATGGCTAGCTCGTGTAGGCAATAATAATGCTCAAGGCGAATATTACTTAACGGAT
CTTATTGCTCTCGCAAACCAAGATAATTGTCAAGTTGTTGCTGTACAAGCAACAGATGTC
ATGGAAGTTGAAGGCGCAAATAATCGCTTACAATTAGCCGCACTTGAACGTTATTTCCAA
AATAAACAAGCCTCCAAATTATTACTTGAAGGCGTAATGATCTACGATCCCGCTCGTTTT
GACCTACGTGGAACATTAGAGCATGGAAAAGATGTGGAAATCGATGTTAATGTTATTATC
GAAGGTAATGTTAAACTCGGTGATCGCGTAAAAATTGGCACAGGTTGCGTATTGAAAAAT
GTTGTTATTGGCAATGATGTAGAAATAAAACCCTATTCAGTGCTAGAGGATTCTATAGTA
GGAGAAAAAGCCGCAATTGGCCCATTTTCTCGTTTACGCCCAGGTGCAGAACTTGCAGCT
GAAACGCATGTCGGTAACTTTGTAGAAATTAAAAAATCTACCGTTGGTAAAGGTTCTAAA
GTAAATCACCTGACCTATGTTGGCGATTCAGAAATTGGCTCAAATTGTAATATTGGAGCG
GGTGTCATAACCTGCAACTACGATGGTGCAAATAAATTTAAAACGATCATCGGTGATGAT
GTGTTTGTGGGATCTGATACACAATTAGTCGCGCCAGTGAAAGTCGCAAATGGCGCAACT
ATTGGTGCTGGGACTACAATTACACGTGATGTTGGCGAAAATGAATTAGTGATTACAAGA
GTTGCTCAACGACATATTCAAGGTTGGCAACGACCAATAAAGAAAAAATAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP43889
UniProtKB Entry NameGLMU_HAEIN
GenBank Protein ID3212176
GenBank Gene IDL42023
PDB ID(s)2V0H, 2V0I, 2V0J, 2V0K, 2V0L, 2VD4, 2W0V, 2W0W, 4E1K, 4KNR, 4KNX, 4KPX, 4KPZ, 4KQL
KEGG IDhin:HI0642
NCBI Gene ID949691
General References
  1. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty BA, Merrick JM, et al.: Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995 Jul 28;269(5223):496-512. [Article]
  2. Mochalkin I, Lightle S, Zhu Y, Ohren JF, Spessard C, Chirgadze NY, Banotai C, Melnick M, McDowell L: Characterization of substrate binding and catalysis in the potential antibacterial target N-acetylglucosamine-1-phosphate uridyltransferase (GlmU). Protein Sci. 2007 Dec;16(12):2657-66. [Article]
  3. Mochalkin I, Lightle S, Narasimhan L, Bornemeier D, Melnick M, Vanderroest S, McDowell L: Structure of a small-molecule inhibitor complexed with GlmU from Haemophilus influenzae reveals an allosteric binding site. Protein Sci. 2008 Mar;17(3):577-82. doi: 10.1110/ps.073271408. Epub 2008 Jan 24. [Article]
  4. Larsen NA, Nash TJ, Morningstar M, Shapiro AB, Joubran C, Blackett CJ, Patten AD, Boriack-Sjodin PA, Doig P: An aminoquinazoline inhibitor of the essential bacterial cell wall synthetic enzyme GlmU has a unique non-protein-kinase-like binding mode. Biochem J. 2012 Sep 15;446(3):405-13. doi: 10.1042/BJ20120596. [Article]
  5. Doig P, Boriack-Sjodin PA, Dumas J, Hu J, Itoh K, Johnson K, Kazmirski S, Kinoshita T, Kuroda S, Sato TO, Sugimoto K, Tohyama K, Aoi H, Wakamatsu K, Wang H: Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping. Bioorg Med Chem. 2014 Nov 1;22(21):6256-69. doi: 10.1016/j.bmc.2014.08.017. Epub 2014 Sep 16. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
4-chloro-N-(3-methoxypropyl)-N-[(3S)-1-(2-phenylethyl)piperidin-3-yl]benzamideexperimentalunknowntargetDetails