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768  structures 315  species 4  interactions 1035  sequences 9  architectures

Family: Lys (PF00062)

Summary: C-type lysozyme/alpha-lactalbumin family

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This is the Wikipedia entry entitled "Glycoside hydrolase family 22". More...

Glycoside hydrolase family 22 Edit Wikipedia article

In molecular biology, glycoside hydrolase family 22 is a family of glycoside hydrolases.

C-type lysozyme/alpha-lactalbumin family
PDB 1dkj EBI.jpg
bobwhite quail lysozyme
Identifiers
Symbol Lys
Pfam PF00062
Pfam clan CL0037
InterPro IPR001916
PROSITE PDOC00716
SCOP 1e0g
SUPERFAMILY 1e0g
TCDB 9.B.41
CAZy GH22

Glycoside hydrolases EC 3.2.1. are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycoside hydrolases, based on sequence similarity, has led to the definition of >100 different families.[1][2][3] This classification is available on the CAZy(http://www.cazy.org/GH1.html) web site,[4] and also discussed at CAZypedia, an online encyclopedia of carbohydrate active enzymes.[5]

Glycoside hydrolase family 22 CAZY GH_22 comprises lysozyme type C (EC 3.2.1.17) lysozyme type i (EC 3.2.1.17) and alpha-lactalbumins. Asp and/or the carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base.

Alpha-lactalbumin,[6][7] is a milk protein that acts as the regulatory subunit of lactose synthetase, acting to promote the conversion of galactosyltransferase to lactose synthase, which is essential for milk production. In the mammary gland, alpha-lactalbumin changes the substrate specificity of galactosyltransferase from N-acetylglucosamine to glucose.

Lysozymes act as bacteriolytic enzymes by hydrolyzing the beta(1->4) bonds between N-acetylglucosamine and N-acetylmuramic acid in the peptidoglycan of prokaryotic cell walls. It has also been recruited for a digestive role in certain ruminants and colobine monkeys.[8] There are at least five different classes of lysozymes:[9] C (chicken type), G (goose type), phage-type (T4), fungi (Chalaropsis), and bacterial (Bacillus subtilis). There are few similarities in the sequences of the different types of lysozymes.

Lysozyme type C and alpha-lactalbumin are similar both in terms of primary sequence and structure, and probably evolved from a common ancestral protein.[10] Around 35 to 40% of the residues are conserved in both proteins as well as the positions of the four disulphide bonds. There is, however, no similarity in function. Another significant difference between the two enzymes is that all lactalbumins have the ability to bind calcium,[11] while this property is restricted to only a few lysozymes.[12]

The binding site was deduced using high resolution X-ray structure analysis and was shown to consist of three aspartic acid residues. It was first suggested that calcium bound to lactalbumin stabilised the structure, but recently it has been claimed that calcium controls the release of lactalbumin from the golgi membrane and that the pattern of ion binding may also affect the catalytic properties of the lactose synthetase complex.

References[edit]

  1. ^ Henrissat B, Callebaut I, Mornon JP, Fabrega S, Lehn P, Davies G (1995). "Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 7090–7094. doi:10.1073/pnas.92.15.7090. PMC 41477. PMID 7624375. 
  2. ^ Henrissat B, Davies G (1995). "Structures and mechanisms of glycosyl hydrolases". Structure 3 (9): 853–859. doi:10.1016/S0969-2126(01)00220-9. PMID 8535779. 
  3. ^ Bairoch, A. "Classification of glycosyl hydrolase families and index of glycosyl hydrolase entries in SWISS-PROT". 1999.
  4. ^ Henrissat, B. and Coutinho P.M. "Carbohydrate-Active Enzymes server". 1999.
  5. ^ CAZypedia, an online encyclopedia of carbohydrate-active enzymes.
  6. ^ Shewale JG, Sinha SK, Brew K (April 1984). "Evolution of alpha-lactalbumins. The complete amino acid sequence of the alpha-lactalbumin from a marsupial (Macropus rufogriseus) and corrections to regions of sequence in bovine and goat alpha-lactalbumins". J. Biol. Chem. 259 (8): 4947–56. PMID 6715332. 
  7. ^ Hall L, Campbell PN (1986). "Alpha-lactalbumin and related proteins: a versatile gene family with an interesting parentage". Essays Biochem. 22: 1–26. PMID 3104032. 
  8. ^ Irwin DM, Wilson AC (July 1989). "Multiple cDNA sequences and the evolution of bovine stomach lysozyme". J. Biol. Chem. 264 (19): 11387–93. PMID 2738070. 
  9. ^ Kamei K, Hara S, Ikenaka T, Murao S (November 1988). "Amino acid sequence of a lysozyme (B-enzyme) from Bacillus subtilis YT-25". J. Biochem. 104 (5): 832–6. PMID 3148618. 
  10. ^ Nitta K, Sugai S (June 1989). "The evolution of lysozyme and alpha-lactalbumin". Eur. J. Biochem. 182 (1): 111–8. doi:10.1111/j.1432-1033.1989.tb14806.x. PMID 2731545. 
  11. ^ Stuart DI, Acharya KR, Walker NP, Smith SG, Lewis M, Phillips DC (1986). "Alpha-lactalbumin possesses a novel calcium binding loop". Nature 324 (6092): 84–7. doi:10.1038/324084a0. PMID 3785375. 
  12. ^ Nitta K, Tsuge H, Sugai S, Shimazaki K (November 1987). "The calcium-binding property of equine lysozyme". FEBS Lett. 223 (2): 405–8. doi:10.1016/0014-5793(87)80328-9. PMID 3666156. 

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C-type lysozyme/alpha-lactalbumin family Provide feedback

Alpha-lactalbumin is the regulatory subunit of lactose synthase, changing the substrate specificity of galactosyltransferase from N-acetylglucosamine to glucose. C-type lysozymes are secreted bacteriolytic enzymes that cleave the peptidoglycan of bacterial cell walls. Structure is a multi-domain, mixed alpha and beta fold, containing four conserved disulfide bonds.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001916

O-Glycosyl hydrolases (EC) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [PUBMED:7624375, PUBMED:8535779]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site.

Glycoside hydrolase family 22 CAZY comprises enzymes with two known activities; lysozyme type C (EC) and alpha-lactalbumins. Asp and/or the carbonyl oxygen of the C-2 acetamido group of the substrate acts as the catalytic nucleophile/base.

Alpha-lactalbumin [PUBMED:6715332, PUBMED:3104032] is a milk protein that acts as the regulatory subunit of lactose synthetase, acting to promote the conversion of galactosyltransferase to lactose synthase, which is essential for milk production. In the mammary gland, alpha-lactalbumin changes the substrate specificity of galactosyltransferase from N-acetylglucosamine to glucose.

Lysozymes (EC) act as bacteriolytic enzymes by hydrolyzing the beta(1->4) bonds between N-acetylglucosamine and N-acetylmuramic acid in the peptidoglycan of prokaryotic cell walls. It has also been recruited for a digestive role in certain ruminants and colobine monkeys [PUBMED:2738070]. There are at least five different classes of lysozymes [PUBMED:3148618]: C (chicken type), G (goose type), phage-type (T4), fungi (Chalaropsis), and bacterial (Bacillus subtilis). There are few similarities in the sequences of the different types of lysozymes.

Lysozyme type C and alpha-lactalbumin are similar both in terms of primary sequence and structure, and probably evolved from a common ancestral protein [PUBMED:2731545]. Around 35 to 40% of the residues are conserved in both proteins as well as the positions of the four disulphide bonds. There is, however, no similarity in function. Another significant difference between the two enzymes is that all lactalbumins have the ability to bind calcium [PUBMED:3785375], while this property is restricted to only a few lysozymes [PUBMED:3666156].

The binding site was deduced using high resolution X-ray structure analysis and was shown to consist of three aspartic acid residues. It was first suggested that calcium bound to lactalbumin stabilised the structure, but recently it has been claimed that calcium controls the release of lactalbumin from the golgi membrane and that the pattern of ion binding may also affect the catalytic properties of the lactose synthetase complex.

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 Lysozyme (CL0037), which has the following description:

Barley chitinase, bacterial chitosanase, and lysozymes from phage and animals all hydrolyse related polysaccharides. The proteins little amino-acid similarity, but have a structurally invariant core consisting of two helices and a three-stranded beta-sheet which form the substrate-binding and catalytic cleft [1].

The clan contains the following 12 members:

Glucosaminidase Glyco_hydro_108 Glyco_hydro_19 Glyco_hydro_46 Lys Lysozyme_like Phage_lysozyme REGB_T4 SLT SLT_2 TraH_2 Transglycosylas

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...

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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
(21)
Full
(1035)
Representative proteomes NCBI
(1346)
Meta
(9)
RP15
(50)
RP35
(75)
RP55
(177)
RP75
(356)
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Format an alignment

  Seed
(21)
Full
(1035)
Representative proteomes NCBI
(1346)
Meta
(9)
RP15
(50)
RP35
(75)
RP55
(177)
RP75
(356)
Alignment:
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Sequence:
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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
(21)
Full
(1035)
Representative proteomes NCBI
(1346)
Meta
(9)
RP15
(50)
RP35
(75)
RP55
(177)
RP75
(356)
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 View help on the curation process

Seed source: Overington and HMM_iterative_training
Previous IDs: lys;
Type: Domain
Author: Eddy SR
Number in seed: 21
Number in full: 1035
Average length of the domain: 110.30 aa
Average identity of full alignment: 37 %
Average coverage of the sequence by the domain: 77.66 %

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 20.9 20.9
Trusted cut-off 21.0 20.9
Noise cut-off 20.8 20.8
Model length: 125
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

Glyco_transf_7C Lys Ivy V-set

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 Lys domain has been found. There are 768 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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