This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Burghoorn, H. P.
Right arrow Articles by Perlin, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Burghoorn, H. P.
Right arrow Articles by Perlin, D. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 2002, p. 615-624, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.615-624.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Molecular Evaluation of the Plasma Membrane Proton Pump from Aspergillus fumigatus

Henriette P. Burghoorn, Patricia Soteropoulos, Padmaja Paderu, Ryota Kashiwazaki, and David S. Perlin*

Public Health Research Institute, New York, New York 10016

Received 8 August 2001/ Returned for modification 1 October 2001/ Accepted 27 November 2001

The gene encoding the plasma membrane proton pump (H+-ATPase) of Aspergillus fumigatus, PMA1, was characterized from A. fumigatus strain NIH 5233 and clinical isolate H11-20. An open reading frame of 3,109 nucleotides with two introns near the N terminus predicts a protein consisting of 989 amino acids with a molecular mass of approximately 108 kDa. The predicted A. fumigatus enzyme is 89 and 51% identical to H+- ATPases of Aspergillus nidulans and Saccharomyces cerevisiae, respectively. The A. fumigatus PMA1 is a typical member of the P-type ATPase family that contains 10 predicted transmembrane segments and conserved sequence motifs TGES, CSDKTGT, MLTGD, and GDGVN within the catalytic region. The enzyme represents 2% of the total plasma membrane protein, and it is characteristically inhibited by orthovanadate, with a 50% inhibitory concentration of ~1.8 µM. H+-ATPases from Aspergillus spp. contain a highly acidic insertion region of 60 amino acids between transmembrane segments 2 and 3, which was confirmed for the membrane-assembled enzyme with a peptide-derived antibody. An increasing A. fumigatus PMA1 copy number confers enhanced growth in low-pH medium, consistent with its role as a proton pump. These results provide support for the development of the A. fumigatus H+-ATPase as a potential drug discovery target.

* Corresponding author. Mailing address: Public Health Research Institute, 455 First Ave., New York, NY 10016. Phone: (212) 578-0820. Fax: (212) 578-0804. E-mail: perlin{at}phri.nyu.edu.

Antimicrobial Agents and Chemotherapy, March 2002, p. 615-624, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.615-624.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gautam, P., Shankar, J., Madan, T., Sirdeshmukh, R., Sundaram, C. S., Gade, W. N., Basir, S. F., Sarma, P. U. (2008). Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B. Antimicrob. Agents Chemother. 52: 4220-4227 [Abstract] [Full Text]  
  • Arendrup, M. C., Perkhofer, S., Howard, S. J., Garcia-Effron, G., Vishukumar, A., Perlin, D., Lass-Florl, C. (2008). Establishing In Vitro-In Vivo Correlations for Aspergillus fumigatus: the Challenge of Azoles versus Echinocandins. Antimicrob. Agents Chemother. 52: 3504-3511 [Abstract] [Full Text]  
  • Afeltra, J., Vitale, R. G., Mouton, J. W., Verweij, P. E. (2004). Potent Synergistic In Vitro Interaction between Nonantimicrobial Membrane-Active Compounds and Itraconazole against Clinical Isolates of Aspergillus fumigatus Resistant to Itraconazole. Antimicrob. Agents Chemother. 48: 1335-1343 [Abstract] [Full Text]  
  • Nascimento, A. M., Goldman, G. H., Park, S., Marras, S. A. E., Delmas, G., Oza, U., Lolans, K., Dudley, M. N., Mann, P. A., Perlin, D. S. (2003). Multiple Resistance Mechanisms among Aspergillus fumigatus Mutants with High-Level Resistance to Itraconazole. Antimicrob. Agents Chemother. 47: 1719-1726 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»