scholarly journals Multiple Metal Binding Domains Enhance the Zn(II) Selectivity of the Divalent Metal Ion Transporter AztA†

Biochemistry ◽  
2007 ◽  
Vol 46 (39) ◽  
pp. 11057-11068 ◽  
Author(s):  
Tong Liu ◽  
Hermes Reyes-Caballero ◽  
Chenxi Li ◽  
Robert A. Scott ◽  
David P. Giedroc
Keyword(s):  
Metal Binding ◽  
Metal Ion ◽  
Divalent Metal ◽  
Ion Transporter ◽  
Binding Domains ◽  
Divalent Metal Ion

scholarly journals Intestinal divalent metal‐ion transporter‐1 is critical for iron homeostasis but is not required for maintenance of Cu or Zn

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Ali Shawki ◽  
Sarah R Anthony ◽  
Yasuhiro Nose ◽  
Tomasa Barrientos De Renshaw ◽  
Dennis J Thiele ◽  
...  
Keyword(s):  
Metal Ion ◽  
Iron Homeostasis ◽  
Divalent Metal ◽  
Ion Transporter ◽  
Divalent Metal Ion

scholarly journals HK97 gp74 Possesses an α-Helical Insertion in the ββα Fold That Affects Its Metal Binding, cos Site Digestion, and In Vivo Activities

2020 ◽  
Vol 202 (8) ◽  
Author(s):  
Sasha A. Weiditch ◽  
Sarah C. Bickers ◽  
Diane Bona ◽  
Karen L. Maxwell ◽  
Voula Kanelis
Keyword(s):  
Metal Binding ◽  
Metal Ion ◽  
Divalent Metal ◽  
Metal Ion Binding ◽  
Divalent Metal Ions ◽  
Nmr Studies ◽  
Phage Dna ◽  
Divalent Metal Ion ◽  
Phage Morphogenesis

ABSTRACT The last gene in the genome of the bacteriophage HK97 encodes gp74, an HNH endonuclease. HNH motifs contain two conserved His residues and an invariant Asn residue, and they adopt a ββα structure. gp74 is essential for phage head morphogenesis, likely because gp74 enhances the specific endonuclease activity of the HK97 terminase complex. Notably, the ability of gp74 to enhance the terminase-mediated cleavage of the phage cos site requires an intact HNH motif in gp74. Mutation of H82, the conserved metal-binding His residue in the HNH motif, to Ala abrogates gp74-mediated stimulation of terminase activity. Here, we present nuclear magnetic resonance (NMR) studies demonstrating that gp74 contains an α-helical insertion in the Ω-loop, which connects the two β-strands of the ββα fold, and a disordered C-terminal tail. NMR data indicate that the Ω-loop insert makes contacts to the ββα fold and influences the ability of gp74 to bind divalent metal ions. Further, the Ω-loop insert and C-terminal tail contribute to gp74-mediated DNA digestion and to gp74 activity in phage morphogenesis. The data presented here enrich our molecular-level understanding of how HNH endonucleases enhance terminase-mediated digestion of the cos site and contribute to the phage replication cycle. IMPORTANCE This study demonstrates that residues outside the canonical ββα fold, namely, the Ω-loop α-helical insert and a disordered C-terminal tail, regulate the activity of the HNH endonuclease gp74. The increased divalent metal ion binding when the Ω-loop insert is removed compared to reduced cos site digestion and phage formation indicates that the Ω-loop insert plays multiple regulatory roles. The data presented here provide insights into the molecular basis of the involvement of HNH proteins in phage DNA packing.

scholarly journals Substrate Profile and Metal-ion Selectivity of Human Divalent Metal-ion Transporter-1

2012 ◽  
Vol 287 (36) ◽  
pp. 30485-30496 ◽  
Author(s):  
Anthony C. Illing ◽  
Ali Shawki ◽  
Christopher L. Cunningham ◽  
Bryan Mackenzie
Keyword(s):  
Metal Ion ◽  
Ion Selectivity ◽  
Divalent Metal ◽  
Ion Transporter ◽  
Divalent Metal Ion ◽  
Metal Ion Selectivity

scholarly journals Calcium-channel blockers do not affect iron transport mediated by divalent metal-ion transporter-1

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4148-4149 ◽  
Author(s):  
Bryan Mackenzie ◽  
Ali Shawki ◽  
Andrew J. Ghio ◽  
Jacqueline D. Stonehuerner ◽  
Lin Zhao ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Metal Ion ◽  
Iron Transport ◽  
Divalent Metal ◽  
Channel Blockers ◽  
Ion Transporter ◽  
Divalent Metal Ion

scholarly journals Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation

BioMetals ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 787-793 ◽  
Author(s):  
Michael D. Garrick ◽  
Lin Zhao ◽  
Jerome A. Roth ◽  
Houbo Jiang ◽  
Jian Feng ◽  
...  
Keyword(s):  
Metal Ion ◽  
Proteasomal Degradation ◽  
Divalent Metal ◽  
Ion Transporter ◽  
Divalent Metal Ion ◽  
Specific Regulation

scholarly journals Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1)

2007 ◽  
Vol 403 (1) ◽  
pp. 59-69 ◽  
Author(s):  
Bryan Mackenzie ◽  
Hitomi Takanaga ◽  
Nadia Hubert ◽  
Andreas Rolfs ◽  
Matthias A. Hediger
Keyword(s):  
Plasma Membrane ◽  
Functional Properties ◽  
Metal Ion ◽  
Cell Types ◽  
Divalent Metal ◽  
The Body ◽  
Ion Transporter ◽  
Voltage Dependent ◽  
Divalent Metal Ion ◽  
Responsive Element

DMT1 (divalent metal-ion transporter 1) is a widely expressed metal-ion transporter that is vital for intestinal iron absorption and iron utilization by most cell types throughout the body, including erythroid precursors. Mutations in DMT1 cause severe microcytic anaemia in animal models. Four DMT1 isoforms that differ in their N- and C-termini arise from mRNA transcripts that vary both at their 5′-ends (starting in exon 1A or exon 1B) and at their 3′-ends giving rise to mRNAs containing (+) or lacking (−) the 3′-IRE (iron-responsive element) and resulting in altered C-terminal coding sequences. To determine whether these variations result in functional differences between isoforms, we explored the functional properties of each isoform using the voltage clamp and radiotracer assays in cRNA-injected Xenopus oocytes. 1A/IRE(+)-DMT1 mediated Fe2+-evoked currents that were saturable (K0.5Fe≈1–2 μM), temperature-dependent (Q10≈2), H+-dependent (K0.5H≈1 μM) and voltage-dependent. 1A/IRE(+)-DMT1 exhibited the provisional substrate profile (ranked on currents) Cd2+, Co2+, Fe2+, Mn2+>Ni2+, V3+≫Pb2+. Zn2+ also evoked large currents; however, the zinc-evoked current was accounted for by H+ and Cl− conductances and was not associated with significant Zn2+ transport. 1B/IRE(+)-DMT1 exhibited the same substrate profile, Fe2+ affinity and dependence on the H+ electrochemical gradient. Each isoform mediated 55Fe2+ uptake and Fe2+-evoked currents at low extracellular pH. Whereas iron transport activity varied markedly between the four isoforms, the activity for each correlated with the density of anti-DMT1 immunostaining in the plasma membrane, and the turnover rate of the Fe2+ transport cycle did not differ between isoforms. Therefore all four isoforms of human DMT1 function as metal-ion transporters of equivalent efficiency. Our results reveal that the N- and C-terminal sequence variations among the DMT1 isoforms do not alter DMT1 functional properties. We therefore propose that these variations serve as tissue-specific signals or cues to direct DMT1 to the appropriate subcellular compartments (e.g. in erythroid cells) or the plasma membrane (e.g. in intestine).

scholarly journals Ablation of intestinal divalent metal‐ion transporter‐1 produces iron‐deficiency anemia

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Ali Shawki ◽  
Sarah R Anthony ◽  
Eric J Niespodzany ◽  
Avni A Amratia ◽  
Bryan Mackenzie
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Metal Ion ◽  
Divalent Metal ◽  
Deficiency Anemia ◽  
Ion Transporter ◽  
Divalent Metal Ion
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