TY  - JOUR
AU  - Havukainen, H.
AU  - Haataja, S.
AU  - Kauko, A.
AU  - Pulliainen, A. T.
AU  - Salminen, A.
AU  - Haikarainen, T.
AU  - Finne, J.
AU  - Papageorgiou, A. C.
AU  - DESY
TI  - Structural basis of zinc- and terbium-mediated inhibition of ferroxidase activity in Dps ferritin-like proteins
JO  - Protein science
VL  - 17
SN  - 0961-8368
CY  - Hoboken, NJ
PB  - Wiley
M1  - PHPPUBDB-8588
SP  - 1513-1521
PY  - 2008
AB  - Streptococcus suis Dpr is an iron-binding protein involved in oxidative stress resistance. It belongs to the bacterial Dps protein family whose members form dodecameric assemblies. Previous studies have shown that zinc and terbium inhibit iron incorporation in Listeria innocua Dps protein. In order to gain structural insights into the inhibitory effect of zinc and terbium, the crystal structures of Streptococcus suis Dpr complexes with these ions were determined at 1.8 A and 2.1 A, respectively. Both ions were found to bind at the ferroxidase center and in the same location as iron. In addition, a novel zinc-binding site formed by His40 and His44 was identified. Both His residues were found to be present within all known Streptococcus suis Dpr variants and in Streptococcus pneumoniae, Streptococcus gordonii, and Streptococcus sanguinis Dpr proteins. Amino acid sequence alignment of Dpr with other Dps family members revealed that His44 is highly conserved, in contrast to His40. The inhibitory effect of zinc and terbium on iron oxidation in Dpr was studied in vitro, and it was found that both ions at concentrations >0.2 mM almost completely abolish iron binding. These results provide a structural basis for the inhibitory effect of zinc and terbium in the Dps family of proteins, and suggest a potential role of the Dps proteins in zinc detoxification mechanisms involving the second zinc-binding site.
KW  - Amino Acid Sequence
KW  - Bacterial Proteins: chemistry
KW  - Bacterial Proteins: genetics
KW  - Bacterial Proteins: metabolism
KW  - Binding Sites
KW  - Ceruloplasmin: antagonists & inhibitors
KW  - Crystallography, X-Ray
KW  - DNA-Binding Proteins: chemistry
KW  - DNA-Binding Proteins: genetics
KW  - DNA-Binding Proteins: metabolism
KW  - Ferritins: metabolism
KW  - Genes, Bacterial
KW  - Histidine: chemistry
KW  - Humans
KW  - Models, Molecular
KW  - Molecular Sequence Data
KW  - Protein Binding
KW  - Sequence Homology, Amino Acid
KW  - Streptococcus suis: chemistry
KW  - Streptococcus suis: genetics
KW  - Streptococcus suis: isolation & purification
KW  - Streptococcus suis: metabolism
KW  - Terbium: chemistry
KW  - Terbium: metabolism
KW  - Water: chemistry
KW  - Zinc: chemistry
KW  - Zinc: metabolism
KW  - Bacterial Proteins (NLM Chemicals)
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - DPS protein, Bacteria (NLM Chemicals)
KW  - Histidine (NLM Chemicals)
KW  - Terbium (NLM Chemicals)
KW  - Zinc (NLM Chemicals)
KW  - Water (NLM Chemicals)
KW  - Ferritins (NLM Chemicals)
KW  - Ceruloplasmin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:18552126
C2  - pmc:PMC2525527
UR  - <Go to ISI:>//WOS:000258651900006
DO  - DOI:10.1110/ps.036236.108
UR  - https://bib-pubdb1.desy.de/record/85833
ER  -