Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis Journal Article
| Authors: | Buglino, J.; Onwueme, K. C.; Ferreras, J. A.; Quadri, L. E. N.; Lima, C. D. |
| Article Title: | Crystal structure of PapA5, a phthiocerol dimycocerosyl transferase from Mycobacterium tuberculosis |
| Abstract: | Polyketide-associated protein A5 (PapA5) is an acyl-transferase that is involved in production of phthiocerol and phthiodiolone dimycocerosate esters, a class of virulence-enhancing lipids produced by Mycobacterium tuberculosis. Structural analysis of PapA5 at 2.75.Å resolution reveals a two-domain structure that shares unexpected similarity to structures of chloramphenicol acetyltransferase, dihydrolipoyl transacetylase, carnitine acetyltransferase, and VibH, a non-ribosomal peptide synthesis condensation enzyme. The PapA5 active site includes conserved histidine and aspartic acid residues that are critical to PapA5 acyltransferase activity. PapA5 catalyzes acyl transfer reactions on model substrates that contain long aliphatic carbon chains, and two hydrophobic channels were observed linking the PapA5 surface to the active site with properties consistent with these biochemical activities and substrate preferences. An additional α helix not observed in other acyltransferase structures blocks the putative entrance into the PapA5 active site, indicating that conformational changes may be associated with PapA5 activity. PapA5 represents the first structure solved for a protein involved in polyketide synthesis in Mycobacteria. |
| Keywords: | unclassified drug; nonhuman; protein conformation; protein domain; proteins; enzyme activity; structure activity relation; structure-activity relationship; bacteria (microorganisms); bacterial protein; mycobacterium tuberculosis; amino acid sequence; molecular sequence data; sequence homology, amino acid; escherichia coli; recombinant proteins; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; conformational transition; structure analysis; enzyme structure; biochemistry; mycobacterium; corynebacterineae; lipid metabolism; protein structure, secondary; aspartic acid; models, chemical; synthesis (chemical); acyltransferase; acetyltransferases; histidine; enzyme mechanism; esters; carbon; enzyme active site; enzyme conformation; condensation; ester derivative; pyruvate dehydrogenase complex; alpha helix; mycobacteria; acyltransferases; priority journal; article; carnitine acetyltransferase; chloramphenicol acetyltransferase; dihydrolipoyl transacetylase; phthiocerol dimycocerosyl transferase; polyketide associated protein a5; vibh protein; polyketide synthesis; carnitine o-acetyltransferase; chloramphenicol o-acetyltransferase; dihydrolipoyllysine-residue acetyltransferase |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 279 |
| Issue: | 29 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2004-07-16 |
| Start Page: | 30634 |
| End Page: | 30642 |
| Language: | English |
| DOI: | 10.1074/jbc.M404011200 |
| PROVIDER: | scopus |
| PUBMED: | 15123643 |
| DOI/URL: | |
| Notes: | J. Biol. Chem. -- Cited By (since 1996):37 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Source: Scopus |
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