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Title: Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins

Abstract

Zinc acquisition from limited environments is critical for bacterial survival and pathogenesis. AztD has been identified as a periplasmic or cell surface zinc-binding protein in numerous bacterial species. In Paracoccus denitrificans, AztD can transfer zinc directly to AztC, the solute binding protein for a zinc-specific ATP-binding cassette transporter system, suggesting a role in zinc acquisition and homeostasis. Here, we present the first cry stal structures of AztD from P. denitrificans and tbe human pathogen Citrobacter koseri, revealing a beta-propeller fold and two high-affinity zinc-binding sites that are highly conserved among AztD homologs. These structures combined with transfer assays using WT and mutant proteins provide rare insight into the mechanism of direct zinc transfer from one protein to another. Given the importance of zinc import to bacterial pathogenesis, these insights may prove valuable to the development of zinc transfer inhibitors as antibiotics.

Authors:
 [1];  [1]; ORCiD logo [2]; ORCiD logo [1]
  1. New Mexico State Univ., Las Cruces, NM (United States). Dept. of Chemistry and Biochemistry
  2. Reed College, Portland, OR (United States). Dept. of Chemistry
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); Howard Hughes Medical Institute
OSTI Identifier:
1624533
Grant/Contract Number:  
AC02-05CH11231; 1R01GM122819-01A
Resource Type:
Accepted Manuscript
Journal Name:
Communications Biology
Additional Journal Information:
Journal Volume: 2; Journal Issue: 1; Journal ID: ISSN 2399-3642
Publisher:
Springer Nature
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Metals; X-ray Crystallography

Citation Formats

Neupane, Durga Prasad, Fullam, Stephanie Hope, Chacón, Kelly Natalia, and Yukl, Erik Thomas. Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins. United States: N. p., 2019. Web. https://doi.org/10.1038/s42003-019-0542-z.
Neupane, Durga Prasad, Fullam, Stephanie Hope, Chacón, Kelly Natalia, & Yukl, Erik Thomas. Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins. United States. https://doi.org/10.1038/s42003-019-0542-z
Neupane, Durga Prasad, Fullam, Stephanie Hope, Chacón, Kelly Natalia, and Yukl, Erik Thomas. Fri . "Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins". United States. https://doi.org/10.1038/s42003-019-0542-z. https://www.osti.gov/servlets/purl/1624533.
@article{osti_1624533,
title = {Crystal structures of AztD provide mechanistic insights into direct zinc transfer between proteins},
author = {Neupane, Durga Prasad and Fullam, Stephanie Hope and Chacón, Kelly Natalia and Yukl, Erik Thomas},
abstractNote = {Zinc acquisition from limited environments is critical for bacterial survival and pathogenesis. AztD has been identified as a periplasmic or cell surface zinc-binding protein in numerous bacterial species. In Paracoccus denitrificans, AztD can transfer zinc directly to AztC, the solute binding protein for a zinc-specific ATP-binding cassette transporter system, suggesting a role in zinc acquisition and homeostasis. Here, we present the first cry stal structures of AztD from P. denitrificans and tbe human pathogen Citrobacter koseri, revealing a beta-propeller fold and two high-affinity zinc-binding sites that are highly conserved among AztD homologs. These structures combined with transfer assays using WT and mutant proteins provide rare insight into the mechanism of direct zinc transfer from one protein to another. Given the importance of zinc import to bacterial pathogenesis, these insights may prove valuable to the development of zinc transfer inhibitors as antibiotics.},
doi = {10.1038/s42003-019-0542-z},
journal = {Communications Biology},
number = 1,
volume = 2,
place = {United States},
year = {2019},
month = {8}
}

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