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35  structures 2359  species 1  interaction 2676  sequences 8  architectures

Family: LpxC (PF03331)

Summary: UDP-3-O-acyl N-acetylglycosamine deacetylase

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This is the Wikipedia entry entitled "UDP-3-O-N-acetylglucosamine deacetylase". More...

UDP-3-O-N-acetylglucosamine deacetylase Edit Wikipedia article

UDP-3-O-acyl N-acetylglycosamine deacetylase
PDB 2go4 EBI.jpg
crystal structure of aquifex aeolicus lpxc complexed with tu-514
Identifiers
Symbol LpxC
Pfam PF03331
Pfam clan CL0329
InterPro IPR004463
SCOP 1nzt
SUPERFAMILY 1nzt
CAZy CE11

In molecular biology, UDP-3-O-N-acetylglucosamine deacetylase (also known as UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase or UDP-3-O-acyl-GlcNAc deacetylase), EC 3.5.1.-, is a bacterial enzyme involved in lipid A biosynthesis.

It is a zinc-dependent metalloamidase that catalyses the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram negative bacteria. It shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds.[1] The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer alpha/beta structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid.[2] This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents.[3]

References[edit]

  1. ^ Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J, Hindsgaul O, Raetz CR, Zhou P (February 2005). "Refined solution structure of the LpxC-TU-514 complex and pKa analysis of an active site histidine: insights into the mechanism and inhibitor design". Biochemistry 44 (4): 1114–26. doi:10.1021/bi047820z. PMID 15667205. 
  2. ^ Whittington DA, Rusche KM, Shin H, Fierke CA, Christianson DW (July 2003). "Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis". Proc. Natl. Acad. Sci. U.S.A. 100 (14): 8146–50. doi:10.1073/pnas.1432990100. PMC 166197. PMID 12819349. 
  3. ^ Shin H, Gennadios HA, Whittington DA, Christianson DW (April 2007). "Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC". Bioorg. Med. Chem. 15 (7): 2617–23. doi:10.1016/j.bmc.2007.01.044. PMID 17296300. 

This article incorporates text from the public domain Pfam and InterPro IPR004463

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

UDP-3-O-acyl N-acetylglycosamine deacetylase Provide feedback

The enzymes in this family catalyse the second step in the biosynthetic pathway for lipid A.

Literature references

  1. Jackman JE, Fierke CA, Tumey LN, Pirrung M, Uchiyama T, Tahir SH, Hindsgaul O, Raetz CR; , J Biol Chem 2000;275:11002-11009.: Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria. Inhibition of diverse UDP-3-O-(r-3-hydroxymyristoyl)-n-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs. PUBMED:10753902 EPMC:10753902


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004463

UDP-3-O-N-acetylglucosamine deacetylases are zinc-dependent metalloamidases that catalyse the second and committed step in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharide (the major constituent of the outer membrane) into the membrane in Gram negative bacteria. LpxC shows no homology to mammalian metalloamidases and is essential for cell viability, making it an important target for the development of novel antibacterial compounds [PUBMED:15667205]. The structure of UDP-3-O-N-acetylglucosamine deacetylase (LpxC) from Aquifex aeolicus has a two-layer alpha/beta structure similar to that of the second domain of ribosomal protein S5, only in LpxC there is a duplication giving two structural repeats of this fold, each repeat being elaborated with additional structures forming the active site. LpxC contains a zinc-binding motif, which resides at the base of an active site cleft and adjacent to a hydrophobic tunnel occupied by a fatty acid [PUBMED:12819349]. This tunnel accounts for the specificity of LpxC toward substrates and inhibitors bearing appropriately positioned 3-O-fatty acid substituents [PUBMED:17296300].

This entry represents the UDP-3-O-N-acetylglucosamine deacetylase family of proteins.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan S5 (CL0329), which has the following description:

This superfamily contains a wide range of families that possess a structure similar to the second domain of ribosomal S5 protein.

The clan contains the following 14 members:

ChlI DNA_mis_repair EFG_IV Fae GHMP_kinases_N IGPD Lon_C LpxC Ribonuclease_P Ribosomal_S5_C RNase_PH Topo-VIb_trans UPF0029 Xol-1_N

Alignments

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Representative proteomes NCBI
(1850)
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RP35
(429)
RP55
(564)
RP75
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  Seed
(10)
Full
(2676)
Representative proteomes NCBI
(1850)
Meta
(2808)
RP15
(209)
RP35
(429)
RP55
(564)
RP75
(672)
Alignment:
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  Seed
(10)
Full
(2676)
Representative proteomes NCBI
(1850)
Meta
(2808)
RP15
(209)
RP35
(429)
RP55
(564)
RP75
(672)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_3666 (release 6.5)
Previous IDs: none
Type: Family
Author: Mifsud W
Number in seed: 10
Number in full: 2676
Average length of the domain: 253.70 aa
Average identity of full alignment: 43 %
Average coverage of the sequence by the domain: 87.84 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 21.0 20.9
Noise cut-off 19.3 19.3
Model length: 277
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

LpxC

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the LpxC domain has been found. There are 35 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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