Unknown

Dataset Information

0

Studies of human 2,4-dienoyl CoA reductase shed new light on peroxisomal ?-oxidation of unsaturated fatty acids.


ABSTRACT: Peroxisomes play an essential role in maintaining fatty acid homeostasis. Although mitochondria are also known to participate in the catabolism of fatty acids via ?-oxidation, differences exist between the peroxisomal and mitochondrial ?-oxidation. Only peroxisomes, but not mitochondrion, can shorten very long chain fatty acids. Here, we describe the crystal structure of a ternary complex of peroxisomal 2,4-dienoyl CoA reductases (pDCR) with hexadienoyl CoA and NADP, as a prototype for comparison with the mitochondrial 2,4-dienoyl CoA reductase (mDCR) to shed light on the differences between the enzymes from the two organelles at the molecular level. Unexpectedly, the structure of pDCR refined to 1.84 Å resolution reveals the absence of the tyrosine-serine pair seen in the active site of mDCR, which together with a lysine and an asparagine have been deemed a hallmark of the SDR family of enzymes. Instead, aspartate hydrogen-bonded to the C? hydroxyl via a water molecule seems to perturb the water molecule for protonation of the substrate. Our studies provide the first structural evidence for participation of water in the DCR-catalyzed reactions. Biochemical studies and structural analysis suggest that pDCRs can catalyze the shortening of six-carbon-long substrates in vitro. However, the K(m) values of pDCR for short chain acyl CoAs are at least 6-fold higher than those for substrates with 10 or more aliphatic carbons. Unlike mDCR, hinge movements permit pDCR to process very long chain polyunsaturated fatty acids.

SUBMITTER: Hua T 

PROVIDER: S-EPMC3436514 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Studies of human 2,4-dienoyl CoA reductase shed new light on peroxisomal β-oxidation of unsaturated fatty acids.

Hua Tian T   Wu Dong D   Ding Wei W   Wang Jiangyun J   Shaw Neil N   Liu Zhi-Jie ZJ  

The Journal of biological chemistry 20120628 34


Peroxisomes play an essential role in maintaining fatty acid homeostasis. Although mitochondria are also known to participate in the catabolism of fatty acids via β-oxidation, differences exist between the peroxisomal and mitochondrial β-oxidation. Only peroxisomes, but not mitochondrion, can shorten very long chain fatty acids. Here, we describe the crystal structure of a ternary complex of peroxisomal 2,4-dienoyl CoA reductases (pDCR) with hexadienoyl CoA and NADP, as a prototype for compariso  ...[more]

Similar Datasets

| S-EPMC1220715 | biostudies-other
| S-EPMC7237503 | biostudies-literature
| S-EPMC6700156 | biostudies-literature
| S-EPMC7267886 | biostudies-literature
| S-EPMC2697383 | biostudies-literature
| S-EPMC1220285 | biostudies-other
| S-EPMC5241743 | biostudies-literature
| S-EPMC8688145 | biostudies-literature
| S-EPMC4225589 | biostudies-literature
| S-EPMC1154027 | biostudies-other