RGD Reference Report - Local changes in the catalytic site of mammalian histidine decarboxylase can affect its global conformation and stability. - Rat Genome Database

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Local changes in the catalytic site of mammalian histidine decarboxylase can affect its global conformation and stability.

Authors: Rodriguez-Caso, C  Rodriguez-Agudo, D  Moya-Garcia, AA  Fajardo, I  Medina, MA  Subramaniam, V  Sanchez-Jimenez, F 
Citation: Rodriguez-Caso C, etal., Eur J Biochem. 2003 Nov;270(21):4376-87.
RGD ID: 2303733
Pubmed: PMID:14622303   (View Abstract at PubMed)

Mature, active mammalian histidine decarboxylase is a dimeric enzyme of carboxy-truncated monomers (approximately 53 kDa). By using a biocomputational approach, we have generated a three-dimensional model of a recombinant 1/512 fragment of the rat enzyme, which shows kinetic constants similar to those of the mature enzyme purified from rodent tissues. This model, together with previous spectroscopic data, allowed us to postulate that the occupation of the catalytic center by the natural substrate, or by substrate-analogs, would induce remarkable changes in the conformation of the intact holoenzyme. To investigate the proposed conformational changes during catalysis, we have carried out electrophoretic, chromatographic and spectroscopic analyses of purified recombinant rat 1/512 histidine decarboxylase in the presence of the natural substrate or substrate-analogs. Our results suggest that local changes in the catalytic site indeed affect the global conformation and stability of the dimeric protein. These results provide insights for new alternatives to inhibit histamine production efficiently in vivo.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
histidine metabolic process  IDA 2303733 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
amino acid binding  IDA 2303733 RGD 
histidine decarboxylase activity  IDA 2303733 RGD 
identical protein binding  IPIHdc (Rattus norvegicus)2303733homodimerizationRGD 
pyridoxal phosphate binding  IDA 2303733 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hdc  (histidine decarboxylase)


Additional Information