4-Hydroxycinnamoyl-CoA:  An Ionizable Probe of the Active Site of the Medium Chain Acyl-CoA Dehydrogenase†

Biochemistry ◽  
2000 ◽  
Vol 39 (1) ◽  
pp. 92-101 ◽  
Author(s):  
Irina Rudik ◽  
Alasdair Bell ◽  
Peter J. Tonge ◽  
Colin Thorpe
Keyword(s):  
Active Site ◽  
Medium Chain ◽  
Chain Acyl

scholarly journals Redox Properties of Human Medium-Chain Acyl-CoA Dehydrogenase, Modulation by Charged Active-Site Amino Acid Residues†

Biochemistry ◽  
1998 ◽  
Vol 37 (41) ◽  
pp. 14605-14612 ◽  
Author(s):  
Gina J. Mancini-Samuelson ◽  
Volker Kieweg ◽  
Kim Marie Sabaj ◽  
Sandro Ghisla ◽  
Marian T. Stankovich
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Redox Properties ◽  
Amino Acid Residues ◽  
Medium Chain ◽  
Chain Acyl

Ring Current Effects in the Active Site of Medium-Chain Acyl-CoA Dehydrogenase Revealed by NMR Spectroscopy

2005 ◽  
Vol 127 (23) ◽  
pp. 8424-8432 ◽  
Author(s):  
Jiaquan Wu ◽  
Alasdair F. Bell ◽  
Andrew A. Jaye ◽  
Peter J. Tonge
Keyword(s):  
Nmr Spectroscopy ◽  
Active Site ◽  
Ring Current ◽  
Medium Chain ◽  
Chain Acyl

scholarly journals Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site

1999 ◽  
Vol 337 (2) ◽  
pp. 225-230 ◽  
Author(s):  
Burkhard KÜCHLER ◽  
Abdel-Ghany ABDEL-GHANY ◽  
Peter BROSS ◽  
Andreas NANDY ◽  
Ihab RASCHED ◽  
...  
Keyword(s):  
Active Site ◽  
Biochemical Characterization ◽  
Genetic Disorder ◽  
Ph Dependence ◽  
Flow Measurements ◽  
Medium Chain ◽  
Prevalent Disease ◽  
Chain Acyl ◽  
Electron Transferring Flavoprotein

Medium-chain acyl-CoA dehydrogenase (MCADH) deficiency, an autosomal recessive inherited disorder, is the most common genetic disorder in mitochondrial β-oxidation in humans. In addition to one prevalent disease-causing mutation (K304E), a series of rarer mutations has been reported, but none of these has yet been characterized in detail. We report here on the biochemical characterization of the purified recombinant mutant protein in which threonine is replaced by alanine at position 168 of the mature protein (T168A-MCADH). It is the first mutation to be found in patients that is located in the active site of the enzyme. Thr-168 is hydrogen-bonded to the flavin N(5) of the cofactor FAD. The thermostability of T168A-MCADH is markedly decreased compared with human wild-type MCADH (hwt-MCADH). Catalytic activity with ferricenium as acceptor is lowered by 80% and with the natural acceptor electron-transferring flavoprotein by over 90% compared with hwt-MCADH. In the mutant the extent of flavin semiquinone formed on reduction is approx. 50% that of hwt-MCADH. The pK reflected by the pH-dependence of Vmax is shifted from approx. 8.2 (hwt-MCADH) to approx. 7 (T168A-MCADH) and the rates of enzyme flavin reduction (stopped-flow measurements) are only approx. 1/10 those of the parent enzyme. These properties are discussed in the light of the possible mechanisms leading to disease in humans.

scholarly journals Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site

1999 ◽  
Vol 337 (2) ◽  
pp. 225 ◽  
Author(s):  
Burkhard KÜCHLER ◽  
Abdel-Ghany ABDEL-GHANY ◽  
Peter BROSS ◽  
Andreas NANDY ◽  
Ihab RASCHED ◽  
...  
Keyword(s):  
Active Site ◽  
Biochemical Characterization ◽  
Medium Chain ◽  
Chain Acyl

Probing Hydrogen-Bonding Interactions in the Active Site of Medium-Chain Acyl-CoA Dehydrogenase Using Raman Spectroscopy†

Biochemistry ◽  
2003 ◽  
Vol 42 (40) ◽  
pp. 11846-11856 ◽  
Author(s):  
Jiaquan Wu ◽  
Alasdair F. Bell ◽  
Lian Luo ◽  
Avery W. Stephens ◽  
Marian T. Stankovich ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Hydrogen Bonding ◽  
Active Site ◽  
Medium Chain ◽  
Hydrogen Bonding Interactions ◽  
Chain Acyl

scholarly journals SOME PROPERTIES OF GLU-376-GLN ACTIVE SITE MUTANT OF HUMAN MEDIUM-CHAIN ACYL-COA DEHYDROGENASE

1991 ◽  
pp. 319-324
Author(s):  
Stefan Engst ◽  
Peter Bross ◽  
Jochen Stiemke ◽  
Andrea Schieber ◽  
Arnold W. Strauss ◽  
...  
Keyword(s):  
Active Site ◽  
Medium Chain ◽  
Chain Acyl
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