RGD Reference Report - Structural determination of the substrate specificities and regioselectivities of the rat and human fatty acid omega-hydroxylases. - Rat Genome Database

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Structural determination of the substrate specificities and regioselectivities of the rat and human fatty acid omega-hydroxylases.

Authors: Hoch, U  Zhang, Z  Kroetz, DL  Ortiz de Montellano, PR 
Citation: Hoch U, etal., Arch Biochem Biophys. 2000 Jan 1;373(1):63-71.
RGD ID: 1625566
Pubmed: PMID:10620324   (View Abstract at PubMed)
DOI: DOI:10.1006/abbi.1999.1504   (Journal Full-text)

The substrate and regiospecificities of the known CYP4A enzymes from rat (CYP4A1, -4A2, -4A3, and -4A8) and human (CYP4A11) have been determined using lauric (C12), myristic (C14), palmitic (C16), oleic (C18:1), and arachidonic (C20:4) acids. The CYP4A2 and CYP4A8 cDNAs required to complete the enzyme set were cloned from a rat kidney library. All five proteins were expressed in Escherichia coli and were purified with the help of a six-histidine tag at the carboxyl terminus. Two complementary CYP4A2-CYP4A3 chimeras fused at residue 119 (CYP4A2) and 122 (CYP4A3) were constructed to explore the roles of the 18 amino acid differences between the parent proteins in determining their catalytic profiles. The chimera in which the first 119 amino acids are from CYP4A2 indicates that the first 120 amino acids control the substrate specificity. The chimera in which the first 122 amino acids are from CYP4A3 is inactive due to a defect in electron transfer to the heme group. The highest activity for lauric acid was obtained with CYP4A1 and CYP4A8, but for all the proteins the activity decreased with increasing fatty acid chain length. The fact that none of the rat and human CYP4A enzymes exhibits a high activity with arachidonic acid appears to limit their role as catalysts for the physiologically important conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE).



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cyp4a2Ratarachidonate binding  IDA  RGD 
Cyp4a2Ratfatty acid binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp4a2  (cytochrome P450, family 4, subfamily a, polypeptide 2)


Additional Information