Summary: Gallidermin

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Wikipedia: Lantibiotics
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This is the Wikipedia entry entitled "Lantibiotics". More...

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Lantibiotics Edit Wikipedia article

Gallidermin

Identifiers

Symbol

Gallidermin

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Lantibiotics are a class of peptide antibiotics that contain the characteristic polycyclic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine and 2-aminoisobutyric acid.

Lanthionine is composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether (monosulphide) linkage.

Lantibiotics are produced by a large number of Gram-positive bacteria such as Streptococcus and Streptomyces to attack other Gram-positive bacteria, and as such, they are considered a member of the bacteriocins. Bacteriocins are classified according to their extent of posttranslational modification. The lantibiotics are a class of more extensively modified bacteriocins, also called Class I bacteriocins. (Bacteriocins for which disulfide bonds are the only modification to the peptide are Class II bacteriocins.)

Lantibiotics are well studied because of the commercial use of these bacteria in the food industry for making dairy products such as cheese.

Nisin and epidermin are members of a family of lantibiotics that bind to a cell wall precursor lipid component of target bacteria and disrupt cell wall production. The duramycin family of lantibiotics binds phosphoethanolamine in the membranes of its target cells and seem to disrupt several physiological functions.

[edit] History

The name lantibiotics was introduced in 1988 as an abbreviation for "lanthionine-containing peptide antibiotics".^[1] The first structures of these antimicrobial agents were produced by pioneering work by Gross and Morell in the late 1960s and early 1970s, thus marking the formal introduction of lantibiotics. Since then, lantibiotics such as nisin have been used auspiciously for food preservation and have yet to encounter significant bacterial resistance. These attributes of lantibiotics have led to more detailed research into their structures and biosynthetic pathways.

[edit] Classification

Type A lantibiotics are long flexible molecules - e.g. nisin, bisin, subtilin, epidermin, gallidermin^[2] Subgroup AI includes mutacin II; subgroup AII includes mutacin I and III.
Type B lantibiotics are globular - e.g. mersacidin.^[3]^[4] actagardine, duramycin, and cinnamycin.^[5]

Some contain 2 peptides, eg haloduracin.^[6]

[edit] Examples

Lantibiotic	Type	Nr of residues	Nr of thioether links	Other links	refs
nisin subtilin	A	34	5	0
gallidermin epidermin	A	21	3	1	^[2]
mersacidin	B	20	4		^[3]
actagardine	B	19	4	0
cinnamycin duramycin	B	19	3	1	^[5]
Sublancin 168	?	37	1	2	^[7]
Plantaricin C	B	27	4	0

(Sublancin may be an S-linked glycopeptide.^[8]

[edit] Biosynthesis

They are synthesised with a leader polypeptide sequence which is only removed during the transport of the molecule out of the synthesising cell. They are synthesized by ribosomes, which distinguishes them from most natural antibiotics, which are synthesized by specialised enzymes.^[9]

[edit] Mechanism of action

Lantibiotics show substantial specificity for some components (e.g. lipid II) of bacterial cell membranes especially of Gram-positive bacteria. Type A lantibiotics kill rapidly by pore formation, type B lantibiotics inhibit peptidoglycan biosynthesis.^[10] for discussion of mechanism of action. They are active in very low concentrations.^[11]

[edit] Application

[edit] Food preservation

Lantibiotics are produced by Gram-positive bacteria and show strong antimicrobial action towards a wide range of other Gram-positive bacteria.^[12] As such they have become attractive candidates for use in food preservation (by inhibiting pathogens that cause food spoilage) and the pharmaceutical industry (to prevent or fight infections in humans or animals).^[12]

[edit] Veterinary antibiotic

Duramycin is used for chickens.

[edit] Clinical antibiotic

One type B lantibiotic NVB302 entered phase 1 clinical trials in 2011 for use against Clostridium difficile,^[13] and reported good results in 2012.^[14]

[edit] Database

BACTIBASE is an open-access database for bacteriocins including lantibiotics.^[15]^[16]

[edit] References

^ Chatterjee C, Paul M, Xie L, van der Donk WA (February 2005). "Biosynthesis and mode of action of lantibiotics". Chem. Rev. 105 (2): 633–84. doi:10.1021/cr030105v. PMID 15700960.
^ ^a ^b Kellner R, Jung G, Hörner T, Zähner H, Schnell N, Entian KD, Götz F (October 1988). "Gallidermin: a new lanthionine-containing polypeptide antibiotic". Eur. J. Biochem. 177 (1): 53–9. doi:10.1111/j.1432-1033.1988.tb14344.x. PMID 3181159.
^ ^a ^b Sass P, Jansen A, Szekat C, Sass V, Sahl HG, Bierbaum G (2008). "The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus". BMC Microbiol. 8: 186. doi:10.1186/1471-2180-8-186. PMC 2592248. PMID 18947397.
^ Brötz H, Bierbaum G, Markus A, Molitor E, Sahl HG (March 1995). "Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism?". Antimicrob. Agents Chemother. 39 (3): 714–9. doi:10.1128/AAC.39.3.714. PMC 162610. PMID 7793878.
^ ^a ^b Makino A, Baba T, Fujimoto K, Iwamoto K, Yano Y, Terada N, Ohno S, Sato SB, Ohta A, Umeda M, Matsuzaki K, Kobayashi T (January 2003). "Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement". J. Biol. Chem. 278 (5): 3204–9. doi:10.1074/jbc.M210347200. PMID 12446685.
^ Cooper LE, McClerren AL, Chary A, van der Donk WA (October 2008). "Structure-activity relationship studies of the two-component lantibiotic haloduracin". Chem. Biol. 15 (10): 1035–45. doi:10.1016/j.chembiol.2008.07.020. PMC 2633096. PMID 18940665.
^ Stein T (May 2005). "Bacillus subtilis antibiotics: structures, syntheses and specific functions". Mol. Microbiol. 56 (4): 845–57. doi:10.1111/j.1365-2958.2005.04587.x. PMID 15853875.
^ Oman TJ, Boettcher JM, Wang H, Okalibe XN, van der Donk WA (February 2011). "Sublancin is not a lantibiotic but an S-linked glycopeptide". Nat. Chem. Biol. 7 (2): 78–80. doi:10.1038/nchembio.509. PMC 3060661. PMID 21196935.
^ Siegers K, Heinzmann S, Entian KD (May 1996). "Biosynthesis of lantibiotic nisin. Posttranslational modification of its prepeptide occurs at a multimeric membrane-associated lanthionine synthetase complex". J. Biol. Chem. 271 (21): 12294–301. PMID 8647829.
^ Brötz H and Sahl H-G. (2000.). "New insights into the mechanism of action of lantibiotics—diverse biological effects by binding to the same molecular target". Journal of Antimicrobial Chemotherapy 46 (1): 1–6. doi:10.1093/jac/46.1.1. PMID 10882681.
^ Cotter, Hill, Ross (2005). Bacterial Lantibiotics: Strategies to Improve Therapeutic Potential 6. Current Protein and Peptide Science. pp. 61–75.
^ ^a ^b van Kraaij C, de Vos WM, Siezen RJ, Kuipers OP (October 1999). "Lantibiotics: biosynthesis, mode of action and applications". Nat Prod Rep 16 (5): 575–87. doi:10.1039/a804531c. PMID 10584332.
^ "New antibiotic compound enters phase I clinical trial". Press Release. Wellcome Trust. 2011-11-03.
^ Parker S (2012-08-06). "Novacta Biosystems Limited completes Phase I study of NVB302 against C. difficile infection in healthy volunteers". Press Release. Celtic Pharma Holding.
^ Hammami R, Zouhir A, Ben Hamida J, Fliss I (2007). "BACTIBASE: a new web-accessible database for bacteriocin characterization". BMC Microbiology 7: 89. doi:10.1186/1471-2180-7-89. PMC 2211298. PMID 17941971.
^ Hammami R, Zouhir A, Le Lay C, Ben Hamida J, Fliss I (2010). "BACTIBASE second release: a database and tool platform for bacteriocin characterization". BMC Microbiology 10: 22. doi:10.1186/1471-2180-10-22. PMC 2824694. PMID 20105292.

[edit] Further reading

Jack R, Bierbaum G, Heidrich C, Sahl HG (September 1995). "The genetics of lantibiotic biosynthesis". Bioessays 17 (9): 793–802. doi:10.1002/bies.950170909. PMID 8763832.
Sahl HG, Jack RW, Bierbaum G (June 1995). "Biosynthesis and biological activities of lantibiotics with unique post-translational modifications". Eur. J. Biochem. 230 (3): 827–53. doi:10.1111/j.1432-1033.1995.0827g.x. PMID 7601145.
Sahl HG, Bierbaum G (1998). "Lantibiotics: biosynthesis and biological activities of uniquely modified peptides from gram-positive bacteria". Annu. Rev. Microbiol. 52: 41–79. doi:10.1146/annurev.micro.52.1.41. PMID 9891793.
Stein T (May 2005). "Bacillus subtilis antibiotics: structures, syntheses and specific functions". Mol. Microbiol. 56 (4): 845–57. doi:10.1111/j.1365-2958.2005.04587.x. PMID 15853875.
Smith JL (2002). Structural and functional characterization of the lantibiotic mutacin (Ph.D.). University of Florida. http://etd.fcla.edu/UF/UFE1001183/smith_jl.pdf.

[edit] External links

"Complete list of lantibiotics". BACTIBASE Database. Functional Proteomics & Alimentary Bio-preservation Research Unit at Institute of Applied Biological Sciences Tunis (ISSBAT), Tunisia.

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.

Gallidermin Provide feedback

No Pfam abstract.

External database links

PANDIT:	PF02052
PRINTS:	PR00323
Pseudofam:	PF02052
SCOP:	1g5q
SYSTERS:	Gallidermin

This tab holds annotation information from the InterPro database.

InterPro entry IPR006079

Lantibiotics are heavily-modified bacteriocin-like peptides from Gram- positive bacteria. They contain alpha,beta-unsaturated amino acids (dehydroalanine and dehydrobutyrine) and lanthionine or 3-methyllanthionine rings (collectively known as thioether rings). There are 2 types of lantibiotic:

Type A (which include nisin, subtilin, epidermin, gallidermin and Pep5) are strongly cationic and bactericidal - nisin, subtilin and Pep5 inhibit the growth of Gram-positive bacteria, probably by voltage-dependent pore formation in the cytoplasmic membrane, resulting in cellular efflux of electrolytes, amino acids and ATP;
Type B lantibiotics possess at most one positive charge and are not bactericidal.

This family contains both type A and type B molecules.

Gene Ontology

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

Biological process

defense response to Gram-positive bacterium (GO:0050830)

Domain organisation

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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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

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You can see the alignments as HTML or in three different sequence viewers:

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You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

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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 (3)	Full (129)	Representative proteomes				NCBI (51)	Meta (1)
	Seed (3)	Full (129)	RP15 (1)	RP35 (2)	RP55 (2)	RP75 (5)	NCBI (51)	Meta (1)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (3)	Full (129)	Representative proteomes				NCBI (51)	Meta (1)
	Seed (3)	Full (129)	RP15 (1)	RP35 (2)	RP55 (2)	RP75 (5)	NCBI (51)	Meta (1)
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 (3)	Full (129)	Representative proteomes				NCBI (51)	Meta (1)
	Seed (3)	Full (129)	RP15 (1)	RP35 (2)	RP55 (2)	RP75 (5)	NCBI (51)	Meta (1)
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.

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:

IPR001049

Previous IDs:

none

Type:

Family

Author:

Mian N, Bateman A

Number in seed:

3

Number in full:

129

Average length of the domain:

45.90 aa

Average identity of full alignment:

56 %

Average coverage of the sequence by the domain:

90.42 %

HMM information

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	20.2	20.2
Trusted cut-off	20.2	20.6
Noise cut-off	19.0	20.1

Model length:

52

Family (HMM) version:

10

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

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kingdom
phylum
class
order
family
genus
species

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As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

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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.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

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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For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

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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.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

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 Gallidermin domain has been found. There are 1 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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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Gallidermin (PF02052)

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