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MtNrdH has been identified as an electron carrier protein in ribonuleotide reduction. Ribonucleotide reduction uses an enzyme called [http://www.proteopedia.org/wiki/index.php/Ribonucleotide_reductase ribonucleotide reductase (RNR)] to make deoxyribonucleotides, which act as precursors to DNA synthesis. Three classes of RNRs have been identified; each class differs in cofactor requirement, structure, and oxygen dependence, but the general catalytic mechanism is conserved in all three classes.<ref name ="Kolberg">Kolberg, M., et al. (2004) Structure, function, and mechanism of ribonucleotide reductases. Biochim. Biophys. Acta 1699 (1−2), 1−34.</ref> Mycobacterium tuberculosis uses class I ribonucleotide reductase.

Class I RNR is further subdivided into class Ia and Ib. Both Ia and Ib reduce ribonucleotide 5’ diphosphate to deoxyribonucleotide 5’ diphosphate (NDP to dNDP). Ribonucleotide reductase utilizes free thiols to reduce NDP to dNDP. After both of the free thiols give up their electrons, they form a disulfide bond. To be able to perform another round of reduction, the disulfide bond needs to be reduced into free thiols again. In class Ia, RNR is reduced by either glutadoxin or thioredoxin, which ~~are first reduced by glutadoxin reductase~~ and ~~thioredoxin reductase, respectively~~.<ref>Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 5th ed. New York: W.H. Freeman, 2008. 888-889.</ref> In class Ib, RNR is reduced by NrdE, which is first reduced by NrdH (Figure 4). Like ~~ribonucleotide reductase~~, NrdE and NrdH both use ~~the making and breaking of~~ disulfide ~~bonds to pass electrons down the chain~~. Thioredoxin reductase uses NADPH to reduce NrdH <ref name="Makhlynets" />. An important distinction between Ia and Ib is that Ia is present in eukaryotes, eubacteria, bacteriophages, and virus, but Ib is only present in eubacteria. <ref name="Kolberg" />

Class I RNR is further subdivided into class Ia and Ib. Both Ia and Ib reduce ribonucleotide 5’ diphosphate to deoxyribonucleotide 5’ diphosphate (NDP to dNDP). Ribonucleotide reductase utilizes free thiols to reduce NDP to dNDP. After both of the free thiols give up their electrons, they form a disulfide bond. To be able to perform another round of reduction, the disulfide bond needs to be reduced into free thiols again. In class Ia, RNR is reduced by either glutadoxin or thioredoxin, which also use disulfide bonds and free thiols to pass electrons.<ref>Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 5th ed. New York: W.H. Freeman, 2008. 888-889.</ref> In class Ib, RNR is reduced by NrdE, which is first reduced by NrdH (Figure 4). Like thioredoxin and glutadoxin, NrdE and NrdH both use a disulfide reduction mechanism (Figure 5). Thioredoxin reductase uses NADPH to reduce NrdH <ref name="Makhlynets" />. An important distinction between Ia and Ib is that Ia is present in eukaryotes, eubacteria, bacteriophages, and virus, but Ib is only present in eubacteria. <ref name="Kolberg" />

[[Image:Ribonucleotide Reduction Class 1b.jpg|thumb|center|upright=2.5|'''Figure 4.'''Ribonucleotide Reduction Class Ib general ~~mechanism~~.<ref name="Makhlynets">Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., & Stubbe, J. (2014). Streptococcus sanguinis Class Ib Ribonucleotide Reductase: HIGH ACTIVITY WITH BOTH IRON AND MANGANESE COFACTORS AND STRUCTURAL INSIGHTS. The Journal of Biological Chemistry, 289(9), 6259–6272. doi:10.1074/jbc.M113.533554.</ref> The role of NrdH is highlighted.]]

[[Image:Ribonucleotide Reduction Class 1b.jpg|thumb|center|upright=2.5|'''Figure 4.'''Ribonucleotide Reduction Class Ib general pathway.<ref name="Makhlynets">Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., & Stubbe, J. (2014). Streptococcus sanguinis Class Ib Ribonucleotide Reductase: HIGH ACTIVITY WITH BOTH IRON AND MANGANESE COFACTORS AND STRUCTURAL INSIGHTS. The Journal of Biological Chemistry, 289(9), 6259–6272. doi:10.1074/jbc.M113.533554.</ref> The role of NrdH is highlighted.]]

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[[Image:NrdH-NrdE disulfide.png|thumb|center|upright=2.5| '''Figure 5.''' The passing of electrons from NrdH to NrdE via disulfide reduction. <ref> Arne Holmgren, Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide, Structure, Volume 3, Issue 3, March 1995, Pages 239-243, ISSN 0969-2126, http://dx.doi.org/10.1016/S0969-2126(01)00153-8. </ref>.]]

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 MtNrdH has been identified as an electron carrier protein in ribonuleotide reduction. Ribonucleotide reduction uses an enzyme called [http://www.proteopedia.org/wiki/index.php/Ribonucleotide_reductase ribonucleotide reductase (RNR)] to make deoxyribonucleotides, which act as precursors to DNA synthesis. Three classes of RNRs have been identified; each class differs in cofactor requirement, structure, and oxygen dependence, but the general catalytic mechanism is conserved in all three classes.<ref name ="Kolberg">Kolberg, M., et al. (2004) Structure, function, and mechanism of ribonucleotide reductases. Biochim. Biophys. Acta 1699 (1−2), 1−34.</ref> Mycobacterium tuberculosis uses class I ribonucleotide reductase.
-Class I RNR is further subdivided into class Ia and Ib. Both Ia and Ib reduce ribonucleotide 5’ diphosphate to deoxyribonucleotide 5’ diphosphate (NDP to dNDP). Ribonucleotide reductase utilizes free thiols to reduce NDP to dNDP. After both of the free thiols give up their electrons, they form a disulfide bond. To be able to perform another round of reduction, the disulfide bond needs to be reduced into free thiols again. In class Ia, RNR is reduced by either glutadoxin or thioredoxin, which are first reduced by glutadoxin reductase and thioredoxin reductase, respectively.<ref>Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 5th   ed. New York: W.H. Freeman, 2008. 888-889.</ref> In class Ib, RNR is reduced by NrdE, which is first reduced by NrdH (Figure 4). Like ribonucleotide reductase, NrdE and NrdH both use the making and breaking of disulfide bonds to pass electrons down the chain. Thioredoxin reductase uses NADPH to reduce NrdH <ref name="Makhlynets" />. An important distinction between Ia and Ib is that Ia is present in eukaryotes, eubacteria, bacteriophages, and virus, but Ib is only present in eubacteria. <ref name="Kolberg" />
+Class I RNR is further subdivided into class Ia and Ib. Both Ia and Ib reduce ribonucleotide 5’ diphosphate to deoxyribonucleotide 5’ diphosphate (NDP to dNDP). Ribonucleotide reductase utilizes free thiols to reduce NDP to dNDP. After both of the free thiols give up their electrons, they form a disulfide bond. To be able to perform another round of reduction, the disulfide bond needs to be reduced into free thiols again. In class Ia, RNR is reduced by either glutadoxin or thioredoxin, which also use disulfide bonds and free thiols to pass electrons.<ref>Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 5th   ed. New York: W.H. Freeman, 2008. 888-889.</ref> In class Ib, RNR is reduced by NrdE, which is first reduced by NrdH (Figure 4). Like thioredoxin and glutadoxin, NrdE and NrdH both use a disulfide reduction mechanism (Figure 5). Thioredoxin reductase uses NADPH to reduce NrdH <ref name="Makhlynets" />. An important distinction between Ia and Ib is that Ia is present in eukaryotes, eubacteria, bacteriophages, and virus, but Ib is only present in eubacteria. <ref name="Kolberg" />
-[[Image:Ribonucleotide Reduction Class 1b.jpg|thumb|center|upright=2.5|'''Figure 4.'''Ribonucleotide Reduction Class Ib general mechanism.<ref name="Makhlynets">Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., & Stubbe, J. (2014). Streptococcus sanguinis Class Ib Ribonucleotide Reductase: HIGH ACTIVITY WITH BOTH IRON AND MANGANESE COFACTORS AND STRUCTURAL INSIGHTS. The Journal of Biological Chemistry, 289(9), 6259–6272. doi:10.1074/jbc.M113.533554.</ref> The role of NrdH is highlighted.]]
+[[Image:Ribonucleotide Reduction Class 1b.jpg|thumb|center|upright=2.5|'''Figure 4.'''Ribonucleotide Reduction Class Ib general pathway.<ref name="Makhlynets">Makhlynets, O., Boal, A. K., Rhodes, D. V., Kitten, T., Rosenzweig, A. C., & Stubbe, J. (2014). Streptococcus sanguinis Class Ib Ribonucleotide Reductase: HIGH ACTIVITY WITH BOTH IRON AND MANGANESE COFACTORS AND STRUCTURAL INSIGHTS. The Journal of Biological Chemistry, 289(9), 6259–6272. doi:10.1074/jbc.M113.533554.</ref> The role of NrdH is highlighted.]]
-[[Image:]]
+[[Image:NrdH-NrdE disulfide.png|thumb|center|upright=2.5| '''Figure 5.''' The passing of electrons from NrdH to NrdE via disulfide reduction. <ref> Arne Holmgren, Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide, Structure, Volume 3, Issue 3, March 1995, Pages 239-243, ISSN 0969-2126, http://dx.doi.org/10.1016/S0969-2126(01)00153-8. </ref>.]]
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