Document Detail


Transcarboxylase: one of nature's early nanomachines.
MedLine Citation:
PMID:  15814455     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The enzyme transcarboxylase (TC) catalyzes an unusual reaction; TC transfers a carboxylate group from methylmalonyl-CoA to pyruvate to form oxaloacetate and propionyl-CoA. Remarkably, to perform this task in Propionii bacteria Nature has created a large assembly made up of 30 polypeptides that totals 1.2 million daltons. In this nanomachine the catalytic machinery is repeated 6-12 times over using ordered arrays of replicated subunits. The latter are sites of the half reactions. On the so-called 12S subunit a biotin cofactor accepts carboxylate, - CO2- , from methylmalonyl-CoA. The carboxylated-biotin then translocates to a second subunit, the 5S, to deliver the carboxylate to pyruvate. We have not yet characterized the intact nanomachine, however, using a battery of biophysical techniques, we have been able to derive novel,and sometimes unexpected, structural and mechanistic insights into the 12S and 5S subunits. Similar insights have been obtained for the small 1.3S subunit that acts as the biotin carrier linking the 12S and 5S forms. Interestingly, some of these insights gained for the 12S and 5S subunits carry over to related mammalian enzymes such as human propionyl-CoA carboxylase and human pyruvate carboxylase, respectively, to provide a rationale for their malfunction in disease-related mutations.
Authors:
Paul R Carey; Frank D Sönnichsen; Vivien C Yee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  IUBMB life     Volume:  56     ISSN:  1521-6543     ISO Abbreviation:  IUBMB Life     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2005-04-07     Completed Date:  2005-06-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  England    
Other Details:
Languages:  eng     Pagination:  575-83     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44120, USA. paul.carey@case.edu
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MeSH Terms
Descriptor/Qualifier:
Acyl Coenzyme A / chemistry
Bacteria / enzymology
Bacterial Proteins / chemistry
Biophysics / methods*
Carboxyl and Carbamoyl Transferases / metabolism,  physiology*
Catalysis
Crystallography, X-Ray
Humans
Magnetic Resonance Spectroscopy
Methylmalonyl-CoA Decarboxylase / chemistry
Models, Biological
Models, Chemical
Models, Molecular
Mutation
Nanotechnology
Oxaloacetate / chemistry
Peptides / chemistry
Pyruvate Carboxylase / chemistry
Pyruvic Acid / chemistry
Spectrum Analysis, Raman
Grant Support
ID/Acronym/Agency:
DK 53053/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Bacterial Proteins; 0/Oxaloacetate; 0/Peptides; 1264-45-5/methylmalonyl-coenzyme A; 127-17-3/Pyruvic Acid; 317-66-8/propionyl-coenzyme A; EC 2.1.3.-/Carboxyl and Carbamoyl Transferases; EC 2.1.3.1/Methylmalonyl-CoA carboxytransferase; EC 4.1.1.41/Methylmalonyl-CoA Decarboxylase; EC 6.4.1.1/Pyruvate Carboxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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