Organization of the multifunctional enzyme type 1

Interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity

Tiila-Riikka Kiema, Jukka Taskinen, Päivi Pirilä, Kari Koivuranta, Rik Wierenga, Kalervo Hiltunen

Research output: Contribution to journalArticleScientificpeer-review

17 Citations (Scopus)

Abstract

Rat peroxisomal multifunctional enzyme type 1 (perMFE-1) is a monomeric protein of b-oxidation. We have defined five functional domains (A, B, C, D and E) in the perMFE-1 based on comparison of the amino acid sequence with homologous proteins from databases and structural data of the hydratase-1/isomerases (H1/I) and (3S)-hydroxyacyl-CoA dehydrogenases (HAD). Domain A (residues 1-190) comprises the H1/I fold and catalyses both 2-enoyl-CoA hydratase-1 and D3-D2-enoyl-CoA isomerase reactions. Domain B (residues 191-280) links domain A to the (3S)-dehydrogenase region, which includes both domain C (residues 281-474) and domain D (residues 480-583). Domains C and D carry features of the dinucleotide-binding and the dimerization domains of monofunctional HADs respectively. Domain E (residues 584-722) has sequence similarity to domain D of the perMFE-1, which suggests that it has evolved via partial gene duplication. Experiments with engineered perMFE-1 variants demonstrate that the H1/I competence of domain A requires stabilizing interactions with domains D and E. The variant His-perMFE (residues 288-479)D, in which the domain C is deleted, is stable and has hydratase-1 activity. It is proposed that the extreme C-terminal domain E in perMFE-1 serves the following three functions: (i) participation in the folding of the N-terminus into a functionally competent H1/I fold, (ii) stabilization of the dehydrogenation domains by interaction with the domain D and (iii) the targeting of the perMFE-1 to peroxisomes via its C-terminal tripeptide.
Original languageEnglish
Pages (from-to)433-441
JournalBiochemical Journal
Volume367
Issue number2
DOIs
Publication statusPublished - 2002
MoE publication typeA1 Journal article-refereed

Fingerprint

Multifunctional Enzymes
Hydro-Lyases
Isomerases
Organizations
Enoyl-CoA Hydratase 2
Dodecenoyl-CoA Isomerase
Oxidoreductases
Amino Acid Sequence Homology
Protein Databases
Gene Duplication
Peroxisomes
Dimerization
Coenzyme A
Mental Competency
Dehydrogenation
Rats
Proteins
Stabilization
Genes
Amino Acids

Keywords

  • beta-oxidation
  • lipid metabolism
  • peroxisome
  • protein engineering
  • structure-function

Cite this

Kiema, Tiila-Riikka ; Taskinen, Jukka ; Pirilä, Päivi ; Koivuranta, Kari ; Wierenga, Rik ; Hiltunen, Kalervo. / Organization of the multifunctional enzyme type 1 : Interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity. In: Biochemical Journal. 2002 ; Vol. 367, No. 2. pp. 433-441.
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title = "Organization of the multifunctional enzyme type 1: Interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity",
abstract = "Rat peroxisomal multifunctional enzyme type 1 (perMFE-1) is a monomeric protein of b-oxidation. We have defined five functional domains (A, B, C, D and E) in the perMFE-1 based on comparison of the amino acid sequence with homologous proteins from databases and structural data of the hydratase-1/isomerases (H1/I) and (3S)-hydroxyacyl-CoA dehydrogenases (HAD). Domain A (residues 1-190) comprises the H1/I fold and catalyses both 2-enoyl-CoA hydratase-1 and D3-D2-enoyl-CoA isomerase reactions. Domain B (residues 191-280) links domain A to the (3S)-dehydrogenase region, which includes both domain C (residues 281-474) and domain D (residues 480-583). Domains C and D carry features of the dinucleotide-binding and the dimerization domains of monofunctional HADs respectively. Domain E (residues 584-722) has sequence similarity to domain D of the perMFE-1, which suggests that it has evolved via partial gene duplication. Experiments with engineered perMFE-1 variants demonstrate that the H1/I competence of domain A requires stabilizing interactions with domains D and E. The variant His-perMFE (residues 288-479)D, in which the domain C is deleted, is stable and has hydratase-1 activity. It is proposed that the extreme C-terminal domain E in perMFE-1 serves the following three functions: (i) participation in the folding of the N-terminus into a functionally competent H1/I fold, (ii) stabilization of the dehydrogenation domains by interaction with the domain D and (iii) the targeting of the perMFE-1 to peroxisomes via its C-terminal tripeptide.",
keywords = "beta-oxidation, lipid metabolism, peroxisome, protein engineering, structure-function",
author = "Tiila-Riikka Kiema and Jukka Taskinen and P{\"a}ivi Piril{\"a} and Kari Koivuranta and Rik Wierenga and Kalervo Hiltunen",
year = "2002",
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Organization of the multifunctional enzyme type 1 : Interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity. / Kiema, Tiila-Riikka; Taskinen, Jukka; Pirilä, Päivi; Koivuranta, Kari; Wierenga, Rik; Hiltunen, Kalervo.

In: Biochemical Journal, Vol. 367, No. 2, 2002, p. 433-441.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Organization of the multifunctional enzyme type 1

T2 - Interaction between N- and C-terminal domains is required for the hydratase-1/isomerase activity

AU - Kiema, Tiila-Riikka

AU - Taskinen, Jukka

AU - Pirilä, Päivi

AU - Koivuranta, Kari

AU - Wierenga, Rik

AU - Hiltunen, Kalervo

PY - 2002

Y1 - 2002

N2 - Rat peroxisomal multifunctional enzyme type 1 (perMFE-1) is a monomeric protein of b-oxidation. We have defined five functional domains (A, B, C, D and E) in the perMFE-1 based on comparison of the amino acid sequence with homologous proteins from databases and structural data of the hydratase-1/isomerases (H1/I) and (3S)-hydroxyacyl-CoA dehydrogenases (HAD). Domain A (residues 1-190) comprises the H1/I fold and catalyses both 2-enoyl-CoA hydratase-1 and D3-D2-enoyl-CoA isomerase reactions. Domain B (residues 191-280) links domain A to the (3S)-dehydrogenase region, which includes both domain C (residues 281-474) and domain D (residues 480-583). Domains C and D carry features of the dinucleotide-binding and the dimerization domains of monofunctional HADs respectively. Domain E (residues 584-722) has sequence similarity to domain D of the perMFE-1, which suggests that it has evolved via partial gene duplication. Experiments with engineered perMFE-1 variants demonstrate that the H1/I competence of domain A requires stabilizing interactions with domains D and E. The variant His-perMFE (residues 288-479)D, in which the domain C is deleted, is stable and has hydratase-1 activity. It is proposed that the extreme C-terminal domain E in perMFE-1 serves the following three functions: (i) participation in the folding of the N-terminus into a functionally competent H1/I fold, (ii) stabilization of the dehydrogenation domains by interaction with the domain D and (iii) the targeting of the perMFE-1 to peroxisomes via its C-terminal tripeptide.

AB - Rat peroxisomal multifunctional enzyme type 1 (perMFE-1) is a monomeric protein of b-oxidation. We have defined five functional domains (A, B, C, D and E) in the perMFE-1 based on comparison of the amino acid sequence with homologous proteins from databases and structural data of the hydratase-1/isomerases (H1/I) and (3S)-hydroxyacyl-CoA dehydrogenases (HAD). Domain A (residues 1-190) comprises the H1/I fold and catalyses both 2-enoyl-CoA hydratase-1 and D3-D2-enoyl-CoA isomerase reactions. Domain B (residues 191-280) links domain A to the (3S)-dehydrogenase region, which includes both domain C (residues 281-474) and domain D (residues 480-583). Domains C and D carry features of the dinucleotide-binding and the dimerization domains of monofunctional HADs respectively. Domain E (residues 584-722) has sequence similarity to domain D of the perMFE-1, which suggests that it has evolved via partial gene duplication. Experiments with engineered perMFE-1 variants demonstrate that the H1/I competence of domain A requires stabilizing interactions with domains D and E. The variant His-perMFE (residues 288-479)D, in which the domain C is deleted, is stable and has hydratase-1 activity. It is proposed that the extreme C-terminal domain E in perMFE-1 serves the following three functions: (i) participation in the folding of the N-terminus into a functionally competent H1/I fold, (ii) stabilization of the dehydrogenation domains by interaction with the domain D and (iii) the targeting of the perMFE-1 to peroxisomes via its C-terminal tripeptide.

KW - beta-oxidation

KW - lipid metabolism

KW - peroxisome

KW - protein engineering

KW - structure-function

U2 - 10.1042/BJ20020292

DO - 10.1042/BJ20020292

M3 - Article

VL - 367

SP - 433

EP - 441

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -