Bifunctional protein GlmU

Details

Name
Bifunctional protein GlmU
Synonyms
  • 2.7.7.23
Gene Name
glmU
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
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
Udp-n-acetylglucosamine diphosphorylase activity
Specific 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.
Pfam Domain Function
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
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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB083444-chloro-N-(3-methoxypropyl)-N-[(3S)-1-(2-phenylethyl)piperidin-3-yl]benzamideexperimentalunknownDetails