Originally found in cyanobacteria and clostridia, flavodoxins were discovered over 50 years ago.[4] These proteins evolved from an anaerobic environment, due to selective pressures.Ferredoxin, another redox protein, was the only protein able to be used in this manner. However, when oxygen became present in the environment, iron became limited. Ferredoxin is iron-dependant as well as oxidant-sensitive. Under these limited iron conditions, ferredoxin was no longer preferred. Flavodoxin on the other hand is the opposite of these traits, as it is oxidant-resistant and has iron-free isofunctional counterparts. Therefore, for some time flavodoxin was the primary redox protein. Now however, when ferredoxin and flavodoxin are present in the same genome, ferredoxin is still used but under low iron conditions, flavodoxin is induced.[5]
Structureedit
3-D structure of flavodoxin protein
Three forms of flavodoxin exist: Oxidized, (OX) semiquinone, (SQ) and hydroquinone (HQ). While relatively small (Mw = 15-22 kDa),[6] flavodoxins exist in "long" and "short" chain classifications. Short chain flavodoxins contain between 140 and 180 amino acid residues,[4] while long chain flavodoxins include a 20 amino acid insertion into the last beta-strand. These residues form a loop which may be used to increase the binding affinity of flavin mononucleotide as well as assist in the formation of folded intermediates. However, it is still not certain what the loops true function is. In addition, the flavin mononucleotide is non-covalently bound to the flavodoxin protein and works to shuttle electrons.[4][5]
Medical applicationsedit
Heliobacter pylori (Hp), the most prevalent human gastric pathogen, requires flavodoxins in its essential POR (pyruvate oxidoreductase enzyme complex) [7] used in pyruvate decarboxylation. Most flavodoxins have a large hydrophobic residue such as tryptophan near the FMN, but Hp has an alanine residue instead, allowing for a pocket of solute to form. Current research is being done to identify non toxic, Hp specific flavodoxin inhibitors for the purpose of treating infection.[8]
Mechanismedit
Flavodoxins require a highly negative redox potential to be active. The semiquinone conformation is stabilized by a hydrogen bond to the N-5 position of the flavin. This bond, as well as a common tryptophan residue near the binding site, aid in lowering SQ reactivity. The hydroquinone form is forced into a planar conformation, destabilizing it.[9] Electron transfer occurs at the dimethylbenzene ring of the FMN.
Flavodoxins in Cyanobacteriaedit
(RCF-1) Trigonal form of recombinant oxidized long chain flavodoxin in Anabaena/Nostoc sp. The active site is characterized by a FMN (flavin mono-nucleotide) cofactor highlighted in magenta. SO4 residue highlighted in yellow. As with most flavodoxins, the residues near the binding site are large and hydrophobic.
In cyanobacteria such as Nostocsp., flavodoxins are heterocyst-specific,[10] and used in photosystem 1 to deliver electrons to nitrogenase, as well as reducing N2 and NADP+, nitrogen fixation and H2 formation.[6]
Referencesedit
^Sancho J (April 2006). "Flavodoxins: sequence, folding, binding, function and beyond". Cellular and Molecular Life Sciences. 63 (7–8): 855–864. doi:10.1007/s00018-005-5514-4. PMID 16465441. S2CID 6090402.
^ abPierella Karlusich JJ, Lodeyro AF, Carrillo N (October 2014). "The long goodbye: the rise and fall of flavodoxin during plant evolution". Journal of Experimental Botany. 65 (18): 5161–5178. doi:10.1093/jxb/eru273. PMC4400536. PMID 25009172.
^Freigang J, Diederichs K, Schäfer KP, Welte W, Paul R (February 2002). "Crystal structure of oxidized flavodoxin, an essential protein in Helicobacter pylori". Protein Science. 11 (2): 253–261. doi:10.1110/ps.28602. PMC2373437. PMID 11790835.
^ abcPrakash D, Iyer PR, Suharti S, Walters KA, Santiago-Martinez MG, Golbeck JH, et al. (December 2019). "Structure and function of an unusual flavodoxin from the domain Archaea". Proceedings of the National Academy of Sciences of the United States of America. 116 (51): 25917–25922. Bibcode:2019PNAS..11625917P. doi:10.1073/pnas.1908578116. PMC6926009. PMID 31801875.
^ abHouwman JA, van Mierlo CP (October 2017). "Folding of proteins with a flavodoxin-like architecture". The FEBS Journal. 284 (19): 3145–3167. doi:10.1111/febs.14077. PMID 28380286. S2CID 3933842.
^ abLodeyro AF, Ceccoli RD, Pierella Karlusich JJ, Carrillo N (August 2012). "The importance of flavodoxin for environmental stress tolerance in photosynthetic microorganisms and transgenic plants. Mechanism, evolution and biotechnological potential". FEBS Letters. 586 (18): 2917–2924. doi:10.1016/j.febslet.2012.07.026. PMID 22819831. S2CID 19298219.
^Cremades N, Bueno M, Toja M, Sancho J (April 2005). "Towards a new therapeutic target: Helicobacter pylori flavodoxin". Biophysical Chemistry. 115 (2–3): 267–276. doi:10.1016/j.bpc.2004.12.045. PMID 15752617.
^Salillas S, Sancho J (March 2020). "Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens". International Journal of Molecular Sciences. 21 (5): 1881. doi:10.3390/ijms21051881. PMC7084853. PMID 32164177.
^Simondsen RP, Tollin G (December 1980). "Structure-function relations in flavodoxins". Molecular and Cellular Biochemistry. 33 (1–2): 13–24. doi:10.1007/BF00224568. PMID 6782445. S2CID 24764348.
^Lindberg P, Lindblad P, Cournac L (April 2004). "Gas exchange in the filamentous cyanobacterium Nostoc punctiforme strain ATCC 29133 and Its hydrogenase-deficient mutant strain NHM5". Applied and Environmental Microbiology. 70 (4): 2137–2145. Bibcode:2004ApEnM..70.2137L. doi:10.1128/AEM.70.4.2137-2145.2004. PMC383079. PMID 15066806.
flavodoxin, small, soluble, electron, transfer, proteins, contains, flavin, mononucleotide, prosthetic, group, structure, flavodoxin, characterized, five, stranded, parallel, beta, sheet, surrounded, five, alpha, helices, they, have, been, isolated, from, prok. Flavodoxins Fld are small soluble electron transfer proteins 1 2 Flavodoxins contains flavin mononucleotide as prosthetic group The structure of flavodoxin is characterized by a five stranded parallel beta sheet surrounded by five alpha helices 3 They have been isolated from prokaryotes cyanobacteria and some eukaryotic algae 2 Contents 1 Background 2 Structure 3 Medical applications 4 Mechanism 5 Flavodoxins in Cyanobacteria 6 References 7 External linksBackground editOriginally found in cyanobacteria and clostridia flavodoxins were discovered over 50 years ago 4 These proteins evolved from an anaerobic environment due to selective pressures Ferredoxin another redox protein was the only protein able to be used in this manner However when oxygen became present in the environment iron became limited Ferredoxin is iron dependant as well as oxidant sensitive Under these limited iron conditions ferredoxin was no longer preferred Flavodoxin on the other hand is the opposite of these traits as it is oxidant resistant and has iron free isofunctional counterparts Therefore for some time flavodoxin was the primary redox protein Now however when ferredoxin and flavodoxin are present in the same genome ferredoxin is still used but under low iron conditions flavodoxin is induced 5 Structure edit nbsp 3 D structure of flavodoxin proteinThree forms of flavodoxin exist Oxidized OX semiquinone SQ and hydroquinone HQ While relatively small Mw 15 22 kDa 6 flavodoxins exist in long and short chain classifications Short chain flavodoxins contain between 140 and 180 amino acid residues 4 while long chain flavodoxins include a 20 amino acid insertion into the last beta strand These residues form a loop which may be used to increase the binding affinity of flavin mononucleotide as well as assist in the formation of folded intermediates However it is still not certain what the loops true function is In addition the flavin mononucleotide is non covalently bound to the flavodoxin protein and works to shuttle electrons 4 5 Medical applications editHeliobacter pylori Hp the most prevalent human gastric pathogen requires flavodoxins in its essential POR pyruvate oxidoreductase enzyme complex 7 used in pyruvate decarboxylation Most flavodoxins have a large hydrophobic residue such as tryptophan near the FMN but Hp has an alanine residue instead allowing for a pocket of solute to form Current research is being done to identify non toxic Hp specific flavodoxin inhibitors for the purpose of treating infection 8 Mechanism editFlavodoxins require a highly negative redox potential to be active The semiquinone conformation is stabilized by a hydrogen bond to the N 5 position of the flavin This bond as well as a common tryptophan residue near the binding site aid in lowering SQ reactivity The hydroquinone form is forced into a planar conformation destabilizing it 9 Electron transfer occurs at the dimethylbenzene ring of the FMN Flavodoxins in Cyanobacteria edit nbsp RCF 1 Trigonal form of recombinant oxidized long chain flavodoxin in Anabaena Nostoc sp The active site is characterized by a FMN flavin mono nucleotide cofactor highlighted in magenta SO4 residue highlighted in yellow As with most flavodoxins the residues near the binding site are large and hydrophobic In cyanobacteria such as Nostoc sp flavodoxins are heterocyst specific 10 and used in photosystem 1 to deliver electrons to nitrogenase as well as reducing N2 and NADP nitrogen fixation and H2 formation 6 References edit Sancho J April 2006 Flavodoxins sequence folding binding function and beyond Cellular and Molecular Life Sciences 63 7 8 855 864 doi 10 1007 s00018 005 5514 4 PMID 16465441 S2CID 6090402 a b Pierella Karlusich JJ Lodeyro AF Carrillo N October 2014 The long goodbye the rise and fall of flavodoxin during plant evolution Journal of Experimental Botany 65 18 5161 5178 doi 10 1093 jxb eru273 PMC 4400536 PMID 25009172 Freigang J Diederichs K Schafer KP Welte W Paul R February 2002 Crystal structure of oxidized flavodoxin an essential protein in Helicobacter pylori Protein Science 11 2 253 261 doi 10 1110 ps 28602 PMC 2373437 PMID 11790835 a b c Prakash D Iyer PR Suharti S Walters KA Santiago Martinez MG Golbeck JH et al December 2019 Structure and function of an unusual flavodoxin from the domain Archaea Proceedings of the National Academy of Sciences of the United States of America 116 51 25917 25922 Bibcode 2019PNAS 11625917P doi 10 1073 pnas 1908578116 PMC 6926009 PMID 31801875 a b Houwman JA van Mierlo CP October 2017 Folding of proteins with a flavodoxin like architecture The FEBS Journal 284 19 3145 3167 doi 10 1111 febs 14077 PMID 28380286 S2CID 3933842 a b Lodeyro AF Ceccoli RD Pierella Karlusich JJ Carrillo N August 2012 The importance of flavodoxin for environmental stress tolerance in photosynthetic microorganisms and transgenic plants Mechanism evolution and biotechnological potential FEBS Letters 586 18 2917 2924 doi 10 1016 j febslet 2012 07 026 PMID 22819831 S2CID 19298219 Cremades N Bueno M Toja M Sancho J April 2005 Towards a new therapeutic target Helicobacter pylori flavodoxin Biophysical Chemistry 115 2 3 267 276 doi 10 1016 j bpc 2004 12 045 PMID 15752617 Salillas S Sancho J March 2020 Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens International Journal of Molecular Sciences 21 5 1881 doi 10 3390 ijms21051881 PMC 7084853 PMID 32164177 Simondsen RP Tollin G December 1980 Structure function relations in flavodoxins Molecular and Cellular Biochemistry 33 1 2 13 24 doi 10 1007 BF00224568 PMID 6782445 S2CID 24764348 Lindberg P Lindblad P Cournac L April 2004 Gas exchange in the filamentous cyanobacterium Nostoc punctiforme strain ATCC 29133 and Its hydrogenase deficient mutant strain NHM5 Applied and Environmental Microbiology 70 4 2137 2145 Bibcode 2004ApEnM 70 2137L doi 10 1128 AEM 70 4 2137 2145 2004 PMC 383079 PMID 15066806 External links editFlavodoxin at the U S National Library of Medicine Medical Subject Headings MeSH Flavodoxin Folding and Stability Research at Wageningen University the Netherlands The crossovers of flavodoxin at virginia edu Diagram at ohio state edu Retrieved from https en wikipedia org w index php title Flavodoxin amp oldid 1167361685, wikipedia, wiki, book, books, library,
