Summary for peptidase M01.004: leukotriene A4 hydrolase

Summary Gene structure Alignment Tree Sequences Sequence features Distribution Structure Literature Human EST Mouse EST Substrates Inhibitors Pharma

 

Names
MEROPS Nameleukotriene A4 hydrolase
Other namesaminopeptidase T (Sus scropha), LTA4H g.p. (Homo sapiens)
Domain architecture
MEROPS Classification
Classification Clan MA >> Subclan MA(E) >> Family M1 >> Subfamily (none) >> M01.004
Holotypeleukotriene A4 hydrolase (Homo sapiens), Uniprot accession P09960 (peptidase unit: 209-451), MERNUM MER0001013
History Identifier created: Handbook of Proteolytic Enzymes (1998) Academic Press, London.
Activity
Catalytic typeMetallo
PeplistIncluded in the Peplist with identifier PL00126
NC-IUBMBSubclass 3.4 (Peptidases) >> Sub-subclass 3.3.2 () >> Peptidase 3.3.2.6
EnzymologyBRENDA database
Activity statushuman: active (Haeggstrom, 2004)
mouse: active (Wetterholm et al., 1992)
PhysiologyConversion of leukotriene A4 to B4 in inflammation and allergic reactions.
KnockoutGenetically-deficient develop normally and are healthy. They show that the enzyme is required for the production of leukotriene B4 in an in vivo inflammatory response. The deficient mice are resistant to platelet-activating factor, identifying LTB4 as one mediator of the physiological changes seen in systemic shock. However, no in vivo role of the aminopeptidase activity of leukotriene A4 hydrolase was identified (Byrum et al., 1999).
Pharmaceutical relevanceCatalysing the rate-limiting step in leukotriene B4 production, the enzyme represents an attractive target for therapeutic agents to reduce leukotriene B4 concentrations and control inflammation. The enzyme is suggested to be implicated in diseases including inflammatory bowel disease and psoriasis (Askonas et al., 2002).
Pathways KEGGArachidonic acid metabolism
Other databases TREEFAMhttp://www.treefam.org/family/TF300758
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/rScissile bondg/-/-/- (based on 14 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 0 0 0 0 4 3 0 0
Pro 0 0 0 1 0 0 0 0
Ala 0 0 0 2 0 0 0 0
Val 0 0 0 0 0 0 0 0
Leu 0 0 0 1 0 0 0 1
Ile 0 0 0 0 0 0 0 0
Met 0 0 0 1 0 0 0 1
Phe 0 0 0 0 0 1 2 0
Tyr 0 0 0 2 0 0 0 0
Trp 0 0 0 0 0 0 0 0
Ser 0 0 0 0 0 0 0 0
Thr 0 0 0 0 0 0 0 0
Cys 0 0 0 0 0 0 0 0
Asn 0 0 0 0 0 0 0 0
Gln 0 0 0 0 0 0 0 0
Asp 0 0 0 0 0 1 0 0
Glu 0 0 0 0 0 0 0 0
Lys 0 0 0 1 0 0 0 0
Arg 0 0 0 5 0 0 0 0
His 0 0 0 0 1 0 0 0
Human genetics
Gene symbol Locus Megabases Ensembl Entrez gene Gene Cards OMIM
LTA4H 12q22 ENSG00000111144 4048 LTA4H 151570
Mouse genetics
Gene symbol Position Megabases Ensembl Entrez gene MGI
Lta4h 10:C3 ENSMUSG00000015889 16993 MGI:96836