PMID- 10468558
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 18
DP  - 1999 Aug 31
TI  - Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, 
      a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the
      carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty
      acids.
PG  - 10039-44
AB  - In the third step of the alpha-oxidation of 3-methyl-branched fatty acids such as
      phytanic acid, a 2-hydroxy-3-methylacyl-CoA is cleaved into formyl-CoA and a
      2-methyl-branched fatty aldehyde. The cleavage enzyme was purified from the
      matrix protein fraction of rat liver peroxisomes and identified as a protein made
      up of four identical subunits of 63 kDa. Its activity proved to depend on Mg(2+) 
      and thiamine pyrophosphate, a hitherto unrecognized cofactor of alpha-oxidation. 
      Formyl-CoA and 2-methylpentadecanal were identified as reaction products when the
      purified enzyme was incubated with 2-hydroxy-3-methylhexadecanoyl-CoA as the
      substrate. Hence the enzyme catalyzes a carbon-carbon cleavage, and we propose
      calling it 2-hydroxyphytanoyl-CoA lyase. Sequences derived from tryptic peptides 
      of the purified rat protein were used as queries to recover human expressed
      sequence tags from the databases. The composite cDNA sequence of the human lyase 
      contained an ORF of 1,734 bases that encodes a polypeptide with a calculated
      molecular mass of 63,732 Da. Recombinant human protein, expressed in mammalian
      cells, exhibited lyase activity. The lyase displayed homology to a putative
      Caenorhabditis elegans protein that resembles bacterial oxalyl-CoA
      decarboxylases. Similarly to the decarboxylases, a thiamine pyrophosphate-binding
      consensus domain was present in the C-terminal part of the lyase. Although no
      peroxisome targeting signal, neither 1 nor 2, was apparent, transfection
      experiments with constructs encoding green fluorescent protein fused to the
      full-length lyase or its C-terminal pentapeptide indicated that the C terminus of
      the lyase represents a peroxisome targeting signal 1 variant.
FAU - Foulon, V
AU  - Foulon V
AD  - Division of Pharmacology, Department of Molecular Cell Biology, Katholieke
      Universiteit Leuven, Campus Gasthuisberg B-3000 Leuven, Belgium.
FAU - Antonenkov, V D
AU  - Antonenkov VD
FAU - Croes, K
AU  - Croes K
FAU - Waelkens, E
AU  - Waelkens E
FAU - Mannaerts, G P
AU  - Mannaerts GP
FAU - Van Veldhoven, P P
AU  - Van Veldhoven PP
FAU - Casteels, M
AU  - Casteels M
LA  - eng
SI  - GENBANK/AJ131753
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 4.1.- (Carbon-Carbon Lyases)
RN  - EC 4.1.99.- (2-hydroxyphytanoyl-coenzyme A lyase)
RN  - Q57971654Y (Thiamine Pyrophosphate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Caenorhabditis elegans
MH  - Carbon-Carbon Lyases/*genetics/isolation & purification/*metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Databases, Factual
MH  - Expressed Sequence Tags
MH  - Humans
MH  - Kinetics
MH  - Liver/*enzymology
MH  - Male
MH  - Mice
MH  - Microbodies/*enzymology
MH  - Molecular Sequence Data
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Fusion Proteins/metabolism
MH  - Recombinant Proteins/biosynthesis/isolation & purification/metabolism
MH  - Thiamine Pyrophosphate/*metabolism
MH  - Transfection
PMC - PMC17838
EDAT- 1999/09/01 00:00
MHDA- 1999/09/01 00:01
CRDT- 1999/09/01 00:00
PHST- 1999/09/01 00:00 [pubmed]
PHST- 1999/09/01 00:01 [medline]
PHST- 1999/09/01 00:00 [entrez]
AID - 10.1073/pnas.96.18.10039 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10039-44. doi:
      10.1073/pnas.96.18.10039.