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The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme.
J Mol Biol. 1998 Nov 27; 284(2):401-19.JM

Abstract

8-Amino-7-oxononanoate synthase (or 8-amino-7-ketopelargonate synthase; EC 2.3.1.47; AONS) catalyses the decarboxylative condensation of l-alanine and pimeloyl-CoA in the first committed step of biotin biosynthesis. We have cloned, over-expressed and purified AONS from Escherichia coli and determined the crystal structures of the apo and PLP-bound forms of the enzyme. The protein is a symmetrical homodimer with a tertiary structure and active site organisation similar to, but distinct from, those of other PLP-dependent enzymes whose three-dimensional structures are known. The critical PLP-binding lysine of AONS is located at the end of a deep cleft that allows access of the pantothenate arm of pimeloyl-CoA. A cluster of positively charged residues at the entrance to this cleft forms a putative diphosphate binding site for CoA. The structure of E. coli AONS enables identification of the key residues of the PLP-binding site and thus provides a framework with which to understand the biochemical mechanism, which is similar to that catalysed by 5-aminolevulinate synthase and two other alpha-oxoamine synthases. Although AONS has a low overall sequence similarity with the catalytic domains of other alpha-oxoamine synthases, the structure reveals the regions of significant identity to be functionally important. This suggests that the organisation of the conserved catalytic residues in the active site is similar for all enzymes of this sub-class of PLP-dependent enzymes and they share a common mechanism. Knowledge of the three-dimensional structure of AONS will enable characterisation of the structural features of this enzyme sub-family that are responsible for this important type of reaction.

Authors+Show Affiliations

Structural Biochemistry Group, The University of Edinburgh, Swann Building King's Buildings, Mayfield Road, Edinburgh, EH9 3JR, Scotland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9813126

Citation

Alexeev, D, et al. "The Crystal Structure of 8-amino-7-oxononanoate Synthase: a Bacterial PLP-dependent, acyl-CoA-condensing Enzyme." Journal of Molecular Biology, vol. 284, no. 2, 1998, pp. 401-19.
Alexeev D, Alexeeva M, Baxter RL, et al. The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. J Mol Biol. 1998;284(2):401-19.
Alexeev, D., Alexeeva, M., Baxter, R. L., Campopiano, D. J., Webster, S. P., & Sawyer, L. (1998). The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. Journal of Molecular Biology, 284(2), 401-19.
Alexeev D, et al. The Crystal Structure of 8-amino-7-oxononanoate Synthase: a Bacterial PLP-dependent, acyl-CoA-condensing Enzyme. J Mol Biol. 1998 Nov 27;284(2):401-19. PubMed PMID: 9813126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. AU - Alexeev,D, AU - Alexeeva,M, AU - Baxter,R L, AU - Campopiano,D J, AU - Webster,S P, AU - Sawyer,L, PY - 1998/11/14/pubmed PY - 1998/11/14/medline PY - 1998/11/14/entrez SP - 401 EP - 19 JF - Journal of molecular biology JO - J Mol Biol VL - 284 IS - 2 N2 - 8-Amino-7-oxononanoate synthase (or 8-amino-7-ketopelargonate synthase; EC 2.3.1.47; AONS) catalyses the decarboxylative condensation of l-alanine and pimeloyl-CoA in the first committed step of biotin biosynthesis. We have cloned, over-expressed and purified AONS from Escherichia coli and determined the crystal structures of the apo and PLP-bound forms of the enzyme. The protein is a symmetrical homodimer with a tertiary structure and active site organisation similar to, but distinct from, those of other PLP-dependent enzymes whose three-dimensional structures are known. The critical PLP-binding lysine of AONS is located at the end of a deep cleft that allows access of the pantothenate arm of pimeloyl-CoA. A cluster of positively charged residues at the entrance to this cleft forms a putative diphosphate binding site for CoA. The structure of E. coli AONS enables identification of the key residues of the PLP-binding site and thus provides a framework with which to understand the biochemical mechanism, which is similar to that catalysed by 5-aminolevulinate synthase and two other alpha-oxoamine synthases. Although AONS has a low overall sequence similarity with the catalytic domains of other alpha-oxoamine synthases, the structure reveals the regions of significant identity to be functionally important. This suggests that the organisation of the conserved catalytic residues in the active site is similar for all enzymes of this sub-class of PLP-dependent enzymes and they share a common mechanism. Knowledge of the three-dimensional structure of AONS will enable characterisation of the structural features of this enzyme sub-family that are responsible for this important type of reaction. SN - 0022-2836 UR - https://www.unboundmedicine.com/medline/citation/9813126/The_crystal_structure_of_8_amino_7_oxononanoate_synthase:_a_bacterial_PLP_dependent_acyl_CoA_condensing_enzyme_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2836(98)92086-1 DB - PRIME DP - Unbound Medicine ER -