High potential iron-sulfur protein

High potential iron-sulfur protein
File:PDB 1hpi EBI.jpg Structure of the oxidized high-potential iron-sulfur protein.
Identifiers
Symbol	HIPIP
Pfam	PF01355
InterPro	IPR000170
PROSITE	PDOC00515
SCOP	1hpi
SUPERFAMILY	1hpi
OPM superfamily	124
OPM protein	1hpi
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

High potential iron-sulfur proteins (HIPIP) are a specific class of high-redox potential 4Fe-4S ferredoxins that functions in anaerobic electron transport and which occurs in photosynthetic bacteria and in Paracoccus denitrificans. The HiPIPs are small proteins which show significant variation in their sequences, their sizes (from 63 to 85 amino acids), and in their oxidation- reduction potentials. As shown in the following schematic representation the iron-sulfur cluster is bound by four conserved cysteine residues.

                          [ 4Fe-4S cluster]
                          | |       |     |
       xxxxxxxxxxxxxxxxxxxCxCxxxxxxxCxxxxxCxxxx

'C': conserved cysteine involved in the binding of the iron-sulfur cluster.

[Fe₄S₄] clusters

The [Fe₄S₄] clusters are abundant cofactors of metalloproteins. They participate in electron-transfer sequences. The core structure for the [Fe₄S₄] cluster is a cube with alternating Fe and S vertices. These clusters exist in two oxidation states with a small structural change. Two families of [Fe₄S₄] clusters are known: the ferredoxin (Fd) family and the high-potential iron–suflur protein (HiPIP) family. Both HiPIP and Fd share the same resting state: [Fe₄S₄]²⁺, which have the same geometric and spectroscopic features. Differences arise when it comes to their active state: HiPIP forms by oxidation to [Fe₄S₄]³⁺, and Fd is formed by reduction to [Fe₄S₄]⁺.

File:Equation for hipip fd transformation.png

equations on Fd and HiPIP

The different oxidation states are explained by the proteins that combined with the [Fe₄S₄] cluster. Analysis from crystallographic data suggests that HiPIP is capable of preserving its higher oxidation state by forming fewer hydrogen bonds with water. The characteristic fold of the proteins wraps the [Fe₄S₄] cluster in a hydrophobic core, only being able to form about five conserved H-bond to the cluster ligands from the backbone. In contrast, the protein associated with the Fd's allows these clusters to contact solvent resulting in 8 protein H-bonding interactions. The protein binds Fd via conserved CysXXCysXXCys structure (X stands for any amino acid). Also, the unique protein structure and dipolar interactions from peptide and intermolecular water contribute to shielding the [Fe₄S₄]³⁺ cluster from the attack of random outside electron donors, which protects itself from hydrolysis.

Synthetic analogues

HiPIP analogues can be synthesized by ligand exchange reactions of [Fe₄S₄{N(SiMe₃)₂}₄]⁻ with 4 equiv of thiols (HSR) as follows:

[Fe₄S₄{N(SiMe₃)₂}₄]⁻ + 4RSH → [Fe₄S₄(SR)₄]⁻ + 4 HN(SiMe₃)₂

The precursor cluster [Fe₄S₄{N(SiMe₃)₂}₄]⁻ can be synthesized by one-pot reaction of FeCl₃, NaN(SiMe₃)₂, and NaSH. The synthesis of HiPIP analogues can help people understand the factors that cause variety redox of HiPIP.

Biochemical reactions

HiPIPs take part in many oxidizing reactions in creatures, and are especially known with photosynthetic anaerobic bacteria, such as Chromatium, and Ectothiorhodospira. HiPIPs are periplasmic proteins in photosynthetic bacteria. They play a role of electron shuttles in the cyclic electron flow between the photosynthetic reaction center and the cytochrome bc1 complex. Other oxidation reactions HiPIP involved include catalyzing Fe(II) oxidation, being electron donor to reductase and electron accepter for some thiosulfate-oxidizing enzyme.

External links

• PDOC00515 - High potential iron-sulfur proteins in PROSITE

Further reading

This article incorporates text from the public domain Pfam and InterPro IPR000170