High potential iron–sulfur protein

{{Pfam_box | Symbol = HIPIP | Name = High potential iron-sulfur protein | image = PDB_1hpi_EBI.jpg | width = | caption = Structure of the oxidized high-potential iron-sulfur protein.<ref name="pmid8117708">{{Cite journal |vauthors=Benning MM, Meyer TE, Rayment I, Holden HM | title = Molecular Structure of the Oxidized High-Potential Iron-Sulfur Protein Isolated from Ectothiorhodospira vacuolata | doi = 10.1021/bi00175a016 | journal = Biochemistry | volume = 33 | issue = 9 | pages = 2476–2483 | year = 1994 | pmid = 8117708}}</ref> | Pfam= PF01355 | InterPro= IPR000170 | SMART= | PROSITE = PDOC00515 | SCOP = 1hpi | TCDB = | OPM family= 116 | OPM protein= 1hpi | PDB= }}

'''High potential iron-sulfur proteins''' (HIPIP) are a class of iron-sulfur proteins.<ref>{{cite journal |doi=10.1021/cr950045w |title=Protein Control of Redox Potentials of Iron−Sulfur Proteins |date=1996 |last1=Stephens |first1=P. J. |last2=Jollie |first2=D. R. |last3=Warshel |first3=A. |journal=Chemical Reviews |volume=96 |issue=7 |pages=2491–2514 |pmid=11848834 }}</ref> They are ferredoxins that participate in electron transfer in photosynthetic bacteria as well as in ''Paracoccus denitrificans''.

==Structure== The HiPIPs are small proteins, typically containing 63 to 85 amino acid residues. The sequences show significant variation. As shown in the following schematic representation the iron-sulfur cluster is bound by four conserved cysteine residues.<ref name="PUB00002658">{{Cite journal |vauthors=Breiter DR, Meyer TE, Rayment I, Holden HM | title = The molecular structure of the high potential iron-sulfur protein isolated from Ectothiorhodospira halophila determined at 2.5-A resolution | journal = The Journal of Biological Chemistry | volume = 266 | issue = 28 | pages = 18660–18667 | year = 1991 | doi = 10.2210/pdb2hip/pdb | pmid = 1917989 }}</ref>

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

C: conserved cysteine residue involved in the binding of the 4Fe-4S core.<ref>{{cite journal|title=Electron Transfer: Iron-Sulfur Clusters|author=R. H. Holm|journal=Comprehensive Coordination Chemistry II| year=2004|volume=8 |page=61-90}}</ref>

== [Fe₄S₄] clusters== The [Fe₄S₄] clusters are abundant cofactors of metalloproteins.<ref>{{cite journal|first1=Bradley Scott Jr.|last1=Perrin|last2=Ichiye|first2=Toshiko|title=Identifying sequence determinants of reduction potentials of metalloproteins|journal=Biological Inorganic Chemistry|date=2013|volume=18|issue=6|pages=599–608|doi=10.1007/s00775-013-1004-6|pmc=3723707|pmid=23690205}}</ref> 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]⁺.

:<chem title="equations on Fd and HiPIP">\underset{(for\ HiPIP)}{[Fe4S4]^3+} <=>[\ce{oxidation}] \underset{(resting\ state)}{[Fe4S4]^2+} <=>[\ce{reduction}] \underset{(for\ Fd)}{[Fe4S4]+}</chem>

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).<ref>{{cite journal|last1=Dey|first1=Abhishek|last2=Jenney|first2=Francis|last3=Adams|first3=Michael |last4=Babini|first4=Elena|last5=Takahashi|first5=Yasuhiro|last6=Fukuyama|first6=Keiichi|last7=Hodgson|first7=Keith|last8=Hedman|first8=Britt|last9=Solomon|first9=Edward|title=Solvent Tuning of Electrochemical Potentials in the Active Sites of HiPIP Versus Ferredoxin|journal=Science|date=2007|volume=318|issue=5855|pages=1464–1468|doi=10.1126/science.1147753|pmid=18048692|bibcode=2007Sci...318.1464D|s2cid=33046150}}</ref> 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.<ref>{{cite journal|last1=Ohki|first1=Yasuhiro|last2=Tanifuji|first2=Kazuki|last3=Yamada|first3=Norihiro|last4=Imada|first4=Motosuke|last5=Tajima|first5=Tomoyuki|last6=Tatsumi|first6=Kazujuki|title=Synthetic analogues of [Fe4S4(Cys)3(His)] in hydrogenases and [Fe4S4(Cys)4] in HiPIP derived from all-ferric [Fe4S4{N(SiMe3)2}4]|journal=Proceedings of the National Academy of Sciences of the United States of America|date=2011|volume=108|issue=31|pages=12635–12640|doi=10.1073/pnas.1106472108|pmc=3150945|pmid=21768339|doi-access=free}}</ref>

==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.<ref>{{cite book|last1=Valentine|first1=Joan|last2=Bertini|first2=Ivano|last3=Gray|first3=Harry|last4=Stiefel|first4=Edward|title=Biological Inorganic Chemistry: Structure and Reactivity|date=2006-10-30|publisher=University Science Books |isbn=978-1891389436|edition=first}}</ref>

==References== {{reflist}}

==External links== * {{PROSITE|PDOC00515}} - High potential iron-sulfur proteins in PROSITE

==Further reading== *{{Cite journal |vauthors=Nogi T, Fathir I, Kobayashi M, Nozawa T, Miki K | title = Crystal structures of photosynthetic reaction center and high-potential iron-sulfur protein from Thermochromatium tepidum: Thermostability and electron transfer | doi = 10.1073/pnas.240224997 | journal = Proceedings of the National Academy of Sciences | volume = 97 | issue = 25 | pages = 13561–13566 | year = 2000 | pmid = 11095707 | pmc =17615 | bibcode = 2000PNAS...9713561N | doi-access = free }} {{InterPro content|IPR000170}}

{{DEFAULTSORT:High potential iron-sulfur protein}} Category:Protein families Category:Peripheral membrane proteins