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

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

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

UDP-3-O-acyl N-acetylglycosamine deacetylase

crystal structure of aquifex aeolicus lpxc complexed with tu-514

Identifiers

Symbol

LpxC

Pfam clan

1nzt / SCOPe / SUPFAM

CAZy

CE11

Available protein structures:
Pfam Â	structures / ECOD Â
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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

^ Coggins BE, McClerren AL, Jiang L, Li X, Rudolph J, Hindsgaul O, Raetz CR, Zhou P (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): 1114â€“26. doi:10.1021/bi047820z. PMIDÂ 15667205. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Whittington DA, Rusche KM, Shin H, Fierke CA, Christianson DW (2003). "Crystal structure of LpxC, a zinc-dependent deacetylase essential for endotoxin biosynthesis". Proc. Natl. Acad. Sci. U.S.A. 100 (14): 8146â€“50. doi:10.1073/pnas.1432990100. PMCÂ 166197. PMIDÂ 12819349. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Shin H, Gennadios HA, Whittington DA, Christianson DW (2007). "Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC". Bioorg. Med. Chem. 15 (7): 2617â€“23. doi:10.1016/j.bmc.2007.01.044. PMIDÂ 17296300. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

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

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

CAZY:	CE11
SCOP:	1nzt

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase activity (GO:0008759)
Biological process	lipid A biosynthetic process (GO:0009245)

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 18 members:

ChlI DNA_gyraseB DNA_mis_repair EFG_IV Fae GalKase_gal_bdg GHMP_kinases_N IGPD Lon_C LpxC Morc6_S5 Ribonuclease_P Ribosomal_S5_C Ribosomal_S9 RNase_PH Topo-VIb_trans UPF0029 Xol-1_N

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (286)	Full (4671)	Representative proteomes				UniProt (24749)
	Seed (286)	Full (4671)	RP15 (709)	RP35 (2275)	RP55 (4757)	RP75 (8423)	UniProt (24749)
Jalview	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (286)	Full (4671)	Representative proteomes				UniProt (24749)
	Seed (286)	Full (4671)	RP15 (709)	RP35 (2275)	RP55 (4757)	RP75 (8423)	UniProt (24749)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (286)	Full (4671)	Representative proteomes				UniProt (24749)
	Seed (286)	Full (4671)	RP15 (709)	RP35 (2275)	RP55 (4757)	RP75 (8423)	UniProt (24749)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	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.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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.

Note: You can also download the data file for the tree.

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

Seed source:

Pfam-B_3666 (release 6.5)

Previous IDs:

none

Type:

Family

Sequence Ontology:

SO:0100021

Author:

Mifsud W

Number in seed:

286

Number in full:

4671

Average length of the domain:

271 aa

Average identity of full alignment:

40 %

Average coverage of the sequence by the domain:

81.24 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	27.0	27.0
Trusted cut-off	27.2	27.2
Noise cut-off	25.5	26.8

Model length:

268

Family (HMM) version:

16

Download:

download the raw HMM for this family

Species distribution

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How the sunburst is generated

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

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Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

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We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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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 119 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein	Predicted structure	External Information
A0A077ZKL7	View 3D Structure	Click here
A0A0H3GI76	View 3D Structure	Click here
A0A0R0KU41	View 3D Structure	Click here
A0A1D6JU08	View 3D Structure	Click here
A0KPW7	View 3D Structure	Click here
A1AW96	View 3D Structure	Click here
A1K3V2	View 3D Structure	Click here
A1S2G4	View 3D Structure	Click here
A1TKD7	View 3D Structure	Click here
A1VST0	View 3D Structure	Click here
A1WBZ9	View 3D Structure	Click here
A1WI31	View 3D Structure	Click here
A1WYT6	View 3D Structure	Click here
A3MY96	View 3D Structure	Click here
A3QIL6	View 3D Structure	Click here
A4XQT0	View 3D Structure	Click here
A5GA17	View 3D Structure	Click here
A6Q223	View 3D Structure	Click here
A6QBQ9	View 3D Structure	Click here
A6T4N9	View 3D Structure	Click here
A6VQM7	View 3D Structure	Click here
A7GZZ5	View 3D Structure	Click here
A7H914	View 3D Structure	Click here
A7I3V4	View 3D Structure	Click here
A8ALK0	View 3D Structure	Click here
A8EWD3	View 3D Structure	Click here
A8H979	View 3D Structure	Click here
A9AI89	View 3D Structure	Click here
A9BUL2	View 3D Structure	Click here
A9MQB6	View 3D Structure	Click here
B0SS82	View 3D Structure	Click here
B0US73	View 3D Structure	Click here
B1KKX2	View 3D Structure	Click here
B1XT16	View 3D Structure	Click here
B2FPA9	View 3D Structure	Click here
B2IWK6	View 3D Structure	Click here
B2JHF3	View 3D Structure	Click here
B2UCX0	View 3D Structure	Click here
B2VD67	View 3D Structure	Click here
B3PCL2	View 3D Structure	Click here

Showing 40 matches

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Family: LpxC (PF03331)

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