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Title: Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis

Abstract

Pathogenic and opportunistic mycobacteria have a distinct class of non-heme di-iron hemerythrin-like proteins (HLPs). The first to be isolated was the Rv2633c protein, which plays a role in infection by Mycobacterium tuberculosis (Mtb), but could not be crystallized. This work presents the first crystal structure of an ortholog of Rv2633c, the mycobacterial HLP from Mycobacterium kansasii (Mka). This structure differs from those of hemerythrins and other known HLPs. It consists of five α-helices, whereas all other HLP domains have four. In contrast with other HLPs, the HLP domain is not fused to an additional protein domain. The residues ligating and surrounding the di-iron site are also unique among HLPs. Notably, a tyrosine occupies the position normally held by one of the histidine ligands in hemerythrin. This structure was used to construct a homology model of Rv2633c. The structure of five α-helices is conserved and the di-iron site ligands are identical in Rv2633c. Two residues near the ends of helices in the Mka HLP structure are replaced with prolines in the Rv2633c model. This may account for structural perturbations that decrease the solubility of Rv2633c relative to Mka HLP. Clusters of residues that differ in charge or polarity between Rv2633c andmore » Mka HLP that point outward from the helical core could reflect a specificity for potential differential interactions with other protein partners in vivo, which are related to function. The Mka HLP exhibited weaker catalase activity than Rv2633c. Evidence was obtained for the interaction of Mka HLP irons with nitric oxide.« less

Authors:
 [1];  [2]; ORCiD logo [3];  [1]; ORCiD logo [1]
  1. Univ. of Central Florida, Orlando, FL (United States)
  2. UCB Pharma, Bainbridge Island, WA (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Washington State Univ., Pullman, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1599132
Report Number(s):
[PNNL-SA-147766]
[Journal ID: ISSN 0264-6021]
Grant/Contract Number:  
[AC05-76RL01830]
Resource Type:
Accepted Manuscript
Journal Name:
Biochemical Journal
Additional Journal Information:
[ Journal Volume: 477; Journal Issue: 2]; Journal ID: ISSN 0264-6021
Publisher:
Biochemical Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; structural biology; X-ray protein crystallography; tuberculosis; catalase; di-iron; iron; metalloprotein; Mycobacterium tuberculosis; protein structure

Citation Formats

Ma, Zhongxin, Abendroth, Jan, Buchko, Garry W., Rohde, Kyle H., and Davidson, Victor L. Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis. United States: N. p., 2020. Web. doi:10.1042/BCJ20190827.
Ma, Zhongxin, Abendroth, Jan, Buchko, Garry W., Rohde, Kyle H., & Davidson, Victor L. Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis. United States. doi:10.1042/BCJ20190827.
Ma, Zhongxin, Abendroth, Jan, Buchko, Garry W., Rohde, Kyle H., and Davidson, Victor L. Fri . "Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis". United States. doi:10.1042/BCJ20190827. https://www.osti.gov/servlets/purl/1599132.
@article{osti_1599132,
title = {Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis},
author = {Ma, Zhongxin and Abendroth, Jan and Buchko, Garry W. and Rohde, Kyle H. and Davidson, Victor L.},
abstractNote = {Pathogenic and opportunistic mycobacteria have a distinct class of non-heme di-iron hemerythrin-like proteins (HLPs). The first to be isolated was the Rv2633c protein, which plays a role in infection by Mycobacterium tuberculosis (Mtb), but could not be crystallized. This work presents the first crystal structure of an ortholog of Rv2633c, the mycobacterial HLP from Mycobacterium kansasii (Mka). This structure differs from those of hemerythrins and other known HLPs. It consists of five α-helices, whereas all other HLP domains have four. In contrast with other HLPs, the HLP domain is not fused to an additional protein domain. The residues ligating and surrounding the di-iron site are also unique among HLPs. Notably, a tyrosine occupies the position normally held by one of the histidine ligands in hemerythrin. This structure was used to construct a homology model of Rv2633c. The structure of five α-helices is conserved and the di-iron site ligands are identical in Rv2633c. Two residues near the ends of helices in the Mka HLP structure are replaced with prolines in the Rv2633c model. This may account for structural perturbations that decrease the solubility of Rv2633c relative to Mka HLP. Clusters of residues that differ in charge or polarity between Rv2633c and Mka HLP that point outward from the helical core could reflect a specificity for potential differential interactions with other protein partners in vivo, which are related to function. The Mka HLP exhibited weaker catalase activity than Rv2633c. Evidence was obtained for the interaction of Mka HLP irons with nitric oxide.},
doi = {10.1042/BCJ20190827},
journal = {Biochemical Journal},
number = [2],
volume = [477],
place = {United States},
year = {2020},
month = {1}
}

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