?. 20°c, When kept aerobically at 198 room temperature, the activity was stable for at least 10 h (Figure 199 S8). However, when the enzyme was reduced by formate the 200 activity was lost within 4 h of air exposure, and in the absence of 201 nitrate and glycerol the loss occurred in less than 2 h. In contrast, 202 under anaerobic conditions the formate-reduced enzyme 203 maintains its activity even after 48 h (Figure S9). Overall, the 204 oxidized enzyme is highly stable, aerobic conditions did not lead to loss of activity even 197 after 30 days (Figures S6 and S7), vol.49, p.50

, Crystal Structures in Oxidized and Formate-Reduced

, 31 This structure was later reinterpreted 23 revealing, 214 unexpectedly, the dissociation of Sec from metal coordination, 215 and the possible presence of mixed states at the active site. It is 216 thus essential to get additional crystal structures of FDHs, 217 particularly in the reduced state. The DvFdhAB was crystallized 218 aerobically (oxidized form), as well as in an anaerobic chamber 219 in the presence of formate (reduced form). The crystals of the 220 oxidized form (DvFdhAB_ox, 6SDR) diffracted beyond 2.1 Å 221 (Table S2), and the structure was solved by molecular 222 replacement, using the D. gigas FdhAB structure 33 as the search 223 model. The model was traced and refined to final crystallo-224 graphic R work and R free values of 18.6% and 22.6%, respectively, 225 with good geometry. Crystals of the formate-reduced form 226 (DvFdhAB_red, 6SDV) diffracted beyond 1.9 Å, and the 227 structure was solved by molecular replacement using the 228 oxidized form as search model. The model was refined to, States. For a mechanistic understanding of FDHs it is essential 209 to have detailed structural information. There are only a few 210 reported structures, from E. coli FdhH, vol.23, p.31

, The DvFdhAB is a heterodimer (Figure 2) and can be divided 232 into four (FdhA) plus three (FdhB) domains (Figure S10), 233 following the classification of DgFdhAB. The large, catalytic ? 234 subunit harbors the [W(MGD)2, SH, Sec] cofactor and one 235

. 4s]-clusters, The overall structure of the catalytic subunit is very 237 similar to those of DgFdhAB and EcFdhN, with RMSDs of 1, p.30

, Å for 957 ?-carbons and 2.01 Å for 947 ?-carbons, respectively

, Cell 658 disruption and soluble fraction clarification were performed as 659 described above. The soluble fraction was then directly loaded 660 on a Strep-tactin gravity flow (IBA Lifesciences, Germany) 661 column equilibrated with buffer W. After five washing steps with 662 buffer W, the recombinant protein was eluted with buffer W plus 663 2.5 mM D-desthiobiotin. The buffer of eluted samples was 664 exchanged to buffer A and samples were stored, under nitrogen 665 atmosphere, at 4°C for immediate use, or ?80°C for longer 666 periods, For recombinant DvFdhAB affinity purification, cells were 656 resuspended in 100 mM Tris-HCl pH 8.0 with 10% (v/v) 657 glycerol, 10 mM NaNO 3 , and 150 mM NaCl (buffer W)

, Protein concentration was measured with the BCA Protein

, The UV?visible absorption spectra of high purity 671 oxidized sample was acquired on a UV-1800 Shimadzu 672 spectrophotometer, and used to determine the molar extension 673 coefficient. The UV?visible spectrum was also recorded for 674 DvFdhAB after reduction with 20 mM formate, for 30 min, and 675 with 1 mM dithionite, inside the glovebox, Assay Kit from Novagen, with bovine serum albumin as 670 standard

, Thermal Shift Assay. The melting temperature of

, DvFdhAB was determined using the Applied Biosystems 681 Protein Thermal Shift Dye Kit: 1 to 2 mg/mL of pure enzyme, ?6× fold) and the melting curve recorded from 684 25 to 99°C, on the QuantStudio 7 Flex Real-time PCR System 685 from Applied Biosystems, vol.682

, Activity assays were 687 performed with small adaptations from previously reported 688 protocols. 42,43 FDH activity was determined using a UV-1800

, Shimadzu spectrophotometer, inside a COY Anaerobic 690 chamber, with an atmosphere of 2% H 2 /98% N 2 , at room 691 temperature, with stirring. During assay optimization, different 692 preincubations, their time, order of additions, and concen-693 trations were tested

, X-ray diffraction data sets were collected at 100 k using a

, The X-ray diffraction 782 images were integrated with XDS, 65 and data were scaled and 783 merged using CCP4 program Aimless. 66 The crystals of the 784 oxidized form (DvFdhAB_ox) dehydrogenase from Desulfovibrio gigas to build the 789 search model (PDB 1H0H). The two protein sequences share 790 around 64% identity, Pilatus 6M-F detectors on ID29 64 and ID30 64 beamlines at the 781 European Synchrotron Radiation Facility

Å. and B. , 63 Å and diffracted beyond 1.9 Å. 796 The structure was also solved by molecular replacement but 797 using the oxidized form as search model. Model building and 798 refinement were performed with Coot 69 and phenix.refine. 70 799 The refined models for oxidized and reduced forms (PDB 800 entries 6SDR and 6SDV) contain 1177 and 1181 amino acid 801 residues, respectively, and were assessed using Molprobity 802 (Table S2)

, The program CAVER 3.0.1 was used 805 as a PyMOL plugin 71 for calculating the tunnels in DvFdhAB, 806 using manually adjusted settings. The initial starting point (S 807 atom from W-SH), shell depth (2 Å), shell radius (3 Å)

, Sequence Analyses. The amino acid sequence of D

F. Vulgaris, UniProt-Q72EJ1) was used as query search 820 against the UniProt reference proteomes via the Hidden Markov 821 Model (HMM) profile implemented in the Phmmer web 822 server. 72 The search was performed using default parameters 823 and 6063 sequences were found, 75% identity (2599 clusters), 827 and 50% identity, 2019.

. Maximum-likelihood, ML) phylogenetic tree was built 830 based on a multiple sequence alignment of the 608 sequences 831 representing each cluster, performed with the MAFFT 832 software 74 using default options. Fourteen well-known FDH 833 sequences were also included in the alignment (FdnG-1 and 834 FdnG-2 from D. vulgaris

, 837 FdhA from R. capsulatus; FdnG from C. necator; FdhF from T. 838 kivui; FdhF-2 from A. woodii; and FdnG and FdhF from E. coli)

, This work was financially supported by Fundacaõ para a Ciencia 926 e Tecnologia (Portugal) through fellowship SFRH/BD/ 927 116515/2014 (to ARO

/. Fct, . Mctes, and . Feder, , vol.2020

. Poci, Funding from the European Union's Horizon 2020 933 research and innovation programme under grant agreement 934 number 810856 is also acknowledged. The authors are also 935 grateful to the EPR facilities available at the French EPR network 936

A. M. Appel, J. E. Bercaw, A. B. Bocarsly, H. Dobbek, and . Dubois,

D. L. Dupuis, M. Ferry, J. G. Fujita, E. Hille, R. Kenis et al.,

W. Rauchfuss, T. B. Reek, J. N. Seefeldt, L. C. Thauer, R. K. Waldrop et al., Frontiers, Opportunities, and Challenges in 943 Biochemical and Chemical Catalysis of CO 2 Fixation, Chem. Rev, vol.942, issue.8, pp.6621-6658, 2013.

H. Takeda, C. Cometto, O. Ishitani, M. Robert, and . Electrons,

. Photons, Protons and Earth-Abundant Metal Complexes for Molecular 947 Catalysis of CO 2 Reduction, ACS Catal, vol.7, issue.1, pp.70-88, 2017.

J. Shi, Y. Jiang, Z. Jiang, X. Wang, X. Wang et al.,

C. Yang, Enzymatic Conversion of Carbon Dioxide, Chem. Soc. Rev, vol.950, issue.17, pp.5981-6000, 2015.

K. Schuchmann and V. Muller, Autotrophy at the Thermodynamic 952 Limit of Life: A Model for Energy Conservation in Acetogenic Bacteria

, Nat. Rev. Microbiol, vol.12, issue.12, pp.809-821, 2014.

C. A. Cotton and C. Edlich-muth, Bar-Even, A. Reinforcing Carbon 955 Fixation: CO 2 Reduction Replacing and Supporting Carboxylation

, Curr. Opin. Biotechnol, vol.49, pp.49-56, 2018.

M. C. Weiss, F. L. Sousa, N. Mrnjavac, S. Neukirchen, and . Roettger, , p.958

M. Nelson-sathi, S. Martin, and W. F. , The Physiology and Habitat of the 959

P. Arnoux, C. Ruppelt, F. Oudouhou, J. Lavergne, and M. Siponen, , p.1007

I. Toci, R. Mendel, R. R. Bittner, F. Pignol, D. Magalon et al., , 1008.

A. Walburger, Sulphur Shuttling across a Chaperone during 1009

, Molybdenum Cofactor Maturation, Nat. Commun, vol.6, issue.1, p.1010, 2015.

P. Schrapers, T. Hartmann, R. Kositzki, H. Dau, and S. Reschke, , p.1011

C. Schulzke, S. Leimku?ler, M. Haumann, and C. Sulfido, , 1012.

, Ligation Changes at the Molybdenum Cofactor during Substrate 1013

, Conversion by Formate Dehydrogenase (FDH) from Rhodobacter 1014

, Capsulatus. Inorg. Chem, vol.54, issue.7, p.1015, 2015.

W. E. Robinson, A. Bassegoda, E. Reisner, and J. Hirst, , p.1016

, State-Dependent Binding Properties of the Active Site in a Mo-1017

, Containing Formate Dehydrogenase, J. Am. Chem. Soc, vol.2017, issue.29, p.1018

H. C. Raaijmakers, M. J. Romaõ, E. Formate-reduced, and . Coli, , 1020.

, Formate Dehydrogenase H: The Reinterpretation of the Crystal 1021

, Structure Suggests a New Reaction Mechanism. JBIC, p.1022

. Chem, , pp.849-854, 2006.

, Catalytic Workhorse in Bioenergetics, Biochim. Biophys. Acta, Bioenerg, issue.8?9, p.1827, 1026.

C. S. Mota, M. G. Rivas, C. D. Brondino, I. Moura, and J. J. Moura,

G. Gonzalez, P. J. Cerqueira, and N. M. , The Mechanism of 1029 Formate Oxidation by Metal-Dependent Formate Dehydrogenases

, J. Biol. Inorg. Chem, issue.8, pp.1255-1268, 2011.

M. Tiberti, E. Papaleo, N. Russo, L. De-gioia, and G. Zampella,

, Evidence for the Formation of a Mo?H Intermediate in the Catalytic 1033 Cycle of Formate Dehydrogenase, Inorg. Chem, vol.2012, issue.15, pp.8331-1034

N. M. Cerqueira, P. A. Fernandes, and P. J. Gonzalez,

J. J. Moura and M. J. Ramos, The Sulfur Shift: An Activation 1037 Mechanism for Periplasmic Nitrate Reductase and Formate Dehydro-1038 genase, Inorg. Chem, issue.19, p.52, 2013.

T. Hartmann, P. Schrapers, T. Utesch, M. Nimtz, Y. Rippers et al., , 1040.

, Molybdenum Active Site of Formate Dehydrogenase Is Capable of

C. Catalyzing and . Bond, Cleavage and Oxygen Atom Transfer Reactions, Biochemistry, vol.55, issue.16, pp.2381-2389, 1043.

D. Niks, J. Duvvuru, M. Escalona, and R. Hille, Spectroscopic and 1045 Kinetic Properties of the Molybdenum-Containing

, Formate Dehydrogenase from Ralstonia Eutropha, J. Biol. Chem, vol.1047, issue.3, pp.1162-1174, 2016.

G. Dong and U. Ryde, Reaction Mechanism of Formate

, Dehydrogenase Studied by Computational Methods. JBIC

, Inorg. Chem, vol.23, issue.8, pp.1243-1254, 2018.

J. C. Boyington, V. N. Gladyshev, S. V. Khangulov, and . Stadtman,

T. C. Sun and P. D. , Crystal Structure of Formate Dehydrogenase H: 1053 Catalysis Involving Mo, Molybdopterin, Selenocysteine, and an Fe 4 S 4 1054 Cluster, Science, vol.275, issue.5304, pp.1305-1308, 1997.

M. Jormakka, S. Tornroth, B. Byrne, and S. Iwata, Molecular Basis 1056 of Proton Motive Force Generation: Structure of Formate Dehydro-1057 genase-N, Science, vol.295, issue.5561, pp.1863-1871, 2002.

H. Raaijmakers, S. Macieira, J. M. Dias, S. Teixeira, and . Bursakov,

S. Huber, R. Moura, J. J. Moura, I. Romao, and M. J. Gene,

, Formate Dehydrogenase from Desulfovibrio gigas, Structure, vol.10, issue.9, pp.1261-1272, 2002.

G. N. George, C. M. Colangelo, J. Dong, R. Scott, and . Khangulov,

S. V. Gladyshev, V. N. Stadtman, and T. C. X-ray, Absorption 1065 Spectroscopy of the Molybdenum Site of Escherichia coli Formate 1066 Dehydrogenase, J. Am. Chem. Soc, vol.120, issue.35, 1267.

G. N. George, C. Costa, J. J. Moura, and I. Moura, Observation 1068 of Ligand-Based Redox Chemistry at the Active Site of a Molybdenum 1069 Enzyme, J. Am. Chem. Soc, vol.121, issue.36, 1999.

S. V. Khangulov, V. N. Gladyshev, G. C. Dismukes, and . Stadtman,

T. C. , Selenium-Containing Formate Dehydrogenase H from 1072 Escherichia Coli: A Molybdopterin Enzyme That Catalyzes Formate 1073 Oxidation without Oxygen Transfer, Biochemistry, vol.37, issue.10, pp.1074-3518, 1998.

L. B. Maia, I. Moura, and J. J. Moura, EPR Spectroscopy on

, Mononuclear Molybdenum-Containing Enzymes, 2017.

S. Grimaldi, F. Biaso, B. Burlat, and B. Guigliarelli,

, Paramagnetic Resonance Studies of Molybdenum Enzymes, 1080 Molybdenum and Tungsten Enzymes: Spectroscopic and Theoretical 1081 Investigations

R. Hille, C. Schulzke, and M. L. Kirk, , 2016.

M. J. Axley, A. Bock, and T. C. Stadtman, Catalytic Properties of an 1084 Escherichia coli Formate Dehydrogenase Mutant in Which Sulfur 1085 Replaces Selenium, Proc. Natl. Acad. Sci. U. S. A, vol.88, issue.19, pp.8450-1086, 1991.

A. J. Stams and C. M. Plugge, Electron Transfer in Syntrophic 1088 Communities of Anaerobic Bacteria and Archaea, Nat. Rev. Microbiol, vol.7, issue.8, pp.568-577, 1089.

C. M. Plugge, W. Zhang, J. C. Scholten, and A. J. Stams, Metabolic 1091 Flexibility of Sulfate-Reducing Bacteria, Front. Microbiol, 2011.

F. A. De-bok, P. L. Hagedoorn, P. J. Silva, and W. R. Hagen,

E. Schiltz, K. Fritsche, and A. J. Stams, Two W-Containing Formate 1094

, Dehydrogenases (CO 2 -Reductases) Involved in Syntrophic Propionate 1095

, Oxidation by Syntrophobacter f umaroxidans, Eur. J. Biochem, vol.270, issue.11, pp.2476-2485, 2003.

S. M. Da-silva, J. Voordouw, C. Leitaõ, M. Martins, and . Voordouw, , p.1098

G. Pereira and I. A. , Function of Formate Dehydrogenases in 1099

, Desulfovibrio vulgaris Hildenborough Energy Metabolism. Microbiology, vol.1100, issue.8, p.1101, 2013.

S. M. Da-silva, C. Pimentel, and F. M. Valente,

C. Pousada and I. A. Pereira, Tungsten and Molybdenum Regulation of 1103

, Formate Dehydrogenase Expression in Desulfovibrio vulgaris Hilden-1104 borough, J. Bacteriol, vol.193, issue.12, p.1105, 2011.

K. L. Keller, J. D. Wall, and S. Chhabra, Methods for Engineering, p.1106

, Sulfate Reducing Bacteria of the Genus Desulfovibrio, Methods Enzymol, vol.497, p.1108, 1107.

D. Niks and R. Hille, Reductive Activation of CO 2 by Formate 1109

. Dehydrogenases, Methods Enzymol, vol.613, issue.47, p.1110, 2018.

M. J. Almendra, C. D. Brondino, O. Gavel, and A. S. Pereira, , p.1111

P. Tavares, S. Bursakov, R. Duarte, J. Caldeira, and J. J. Moura, , p.1112

I. Moura, Purification and Characterization of a Tungsten-Containing 1113

, Formate Dehydrogenase from Desulfovibrio gigas, Biochemistry, vol.38, issue.49, p.1115, 1999.

A. Bassegoda, C. Madden, D. W. Wakerley, E. Reisner, and J. Hirst, , 1116.

, Reversible Interconversion of CO 2 and Formate by a Molybdenum-1117

, Containing Formate Dehydrogenase, J. Am. Chem. Soc, vol.136, p.1118, 2014.

K. P. Sokol, W. E. Robinson, A. R. Oliveira, and J. Warnan, , vol.1120

M. M. Nowaczyk, A. Ruff, I. A. Pereira, and E. Reisner, Photoreduction 1121 of CO 2 with a Formate Dehydrogenase Driven by Photosystem II Using 1122

, a Semi-Artificial Z-Scheme Architecture. J. Am. Chem. Soc, vol.140, issue.48, pp.16418-16422, 2018.

M. Miller, W. E. Robinson, A. R. Oliveira, and N. Heidary, , p.1125

N. Kornienko, J. Warnan, I. Pereira, and E. Reisner, , 1126.

, Dehydrogenase with Metal Oxides for Reversible Electrocatalysis and 1127

, Solar-Driven Reduction of Carbon Dioxide, Angew. Chem, vol.131, issue.14, p.1129, 2019.

C. Caillet-saguy, P. Turano, M. Piccioli, and G. S. Lukat-rodgers, , p.1130

M. Czjzek, B. Guigliarelli, N. Izadi-pruneyre, and K. R. Rodgers, , p.1131

M. Delepierre and A. Lecroisey, Deciphering the Structural Role of 1132

, Histidine 83 for Heme Binding in Hemophore HasA, J. Biol. Chem, vol.283, issue.52, p.1134, 1133.

S. Duval, J. M. Santini, D. Lemaire, F. Chaspoul, and M. J. Russell, , p.1135

S. Grimaldi and W. Nitschke, , p.1136

, Network Surrounding the Pyranopterins Modulates Redox Coopera-1137

, tivity in the Molybdenum-BisPGD Cofactor in Arsenite Oxidase, p.1138

, Biochim. Biophys. Acta, Bioenerg, issue.9, pp.1353-1362, 2016.

S. Y. Wu, R. A. Rothery, J. H. Weiner, and . Pyranopterin, , 1140.

, Coordination Controls Molybdenum Electrochemistry in Escherichia 1141

. Coli-nitrate-reductase, J. Biol. Chem, vol.54, issue.41, p.1142, 2015.

R. A. Rothery and J. H. Weiner, Shifting the Metallocentric 1143

, Molybdoenzyme Paradigm: The Importance of Pyranopterin Coordi-1144

, J. Biol. Inorg. Chem, vol.20, pp.349-372, 2015.

A. Magalon and P. Ceccaldi, , p.1146

R. Hille, Prokaryotic Mo/W-BisPGD Enzymes Family, RSC Metallobiol-1147 ogy?Molybdenum and Tungsten Enzymes: Biochemistry, p.1148

C. Schulzke and M. L. Kirk, , vol.2017, p.1150, 2017.

M. Zorn, C. H. Ihling, R. Golbik, R. G. Sawers, and A. Sinz, , 1151.

, Selective SelC-Independent Selenocysteine Incorporation into For-1152

, mate Dehydrogenases, vol.8, p.1153, 2013.

S. Ma, R. M. Caprioli, K. E. Hill, and R. F. Burk, Loss of Selenium 1154 from Selenoproteins: Conversion of Selenocysteine to Dehydroalanine 1155

, J. Am. Soc. Mass Spectrom, vol.14, issue.6, p.1156, 2003.

M. C. Marques, C. Tapia, O. Gutie?rez-sanz, and A. R. Ramos, , p.1157

K. L. Keller, J. D. Wall, A. L. De-lacey, P. M. Matias, and I. A. Pereira, , 1158.

, The Direct Role of Selenocysteine, p.1159

C. Maturation, Nat. Chem. Biol, vol.2017, issue.5, p.1160

J. J. Smee, D. C. Goodman, J. H. Reibenspies, and M. Darensbourg,

, Hydrogenases by Iodoacetamide and Iodoacetate, Eur. J. Inorg. Chem, issue.3, pp.539-546, 1999.

R. A. Rothery, B. Stein, M. Solomonson, M. L. Kirk, and J. Weiner,

H. Pyranopterin, Conformation Defines the Function of Molybdenum 1166 and Tungsten Enzymes, Proc. Natl. Acad. Sci. U. S. A, vol.2012, issue.37, pp.1167-14773

D. R. Gisewhite, J. Yang, B. R. Williams, A. Esmail, and B. Stein,

M. L. Kirk and S. J. Burgmayer, Implications of Pyran Cyclization and 1170 Pterin Conformation on Oxidized Forms of the Molybdenum Cofactor

, J. Am. Chem. Soc, vol.140, pp.12808-12818, 2018.

J. G. Jacques, V. Fourmond, P. Arnoux, M. Sabaty, and . Etienne,

E. Grosse, S. Biaso, F. Bertrand, P. Pignol, D. Le?er et al., Reductive Activation in Periplasmic Nitrate Reductase 1175 Involves Chemical Modifications of the Mo-Cofactor beyond the First 1176 Coordination Sphere of the Metal Ion, Biochim. Biophys. Acta, Bioenerg, pp.277-286, 1837.

J. J. Moura, C. D. Brondino, J. Trincao, and M. J. Romao, Mo 1179 and W Bis-MGD Enzymes: Nitrate Reductases and Formate

. Dehydrogenases and . Jbic, J. Biol. Inorg. Chem, vol.9, issue.7, pp.791-799, 2004.

A. A. Mccarthy, R. Barrett, A. Beteva, H. Caserotto, and . Dobias,

F. Felisaz, F. Giraud, T. Guijarro, M. Janocha, R. Khadrouche et al., 1183 et al. ID30B ? a Versatile Beamline for Macromolecular Crystallog-1184 raphy Experiments at the ESRF, J. Synchrotron Radiat, vol.25, issue.4, pp.1185-1249, 2018.

W. X. Kabsch, Acta Crystallogr., Sect. D: Biol. Crystallogr, vol.66, pp.125-132, 1187.

P. R. Evans and G. N. Murshudov, How Good Are My Data and

, What Is the Resolution?, Acta Crystallogr., Sect. D: Biol. Crystallogr, vol.69, pp.1204-1218, 1190.

A. J. Mccoy, R. W. Grosse-kunstleve, P. D. Adams, and M. Winn,

D. Storoni, L. C. Read, and R. J. , Phaser Crystallographic Software. J. Appl

. Crystallogr, , vol.40, pp.658-674, 2007.

N. Stein and . Chainsaw, A Program for Mutating Pdb Files Used 1195 as Templates in Molecular Replacement, J. Appl. Crystallogr, vol.41, pp.1196-641, 2008.

P. Emsley, B. Lohkamp, W. G. Scott, and K. Cowtan, Features and 1198 Development of Coot, Acta Crystallogr., Sect. D: Biol. Crystallogr, pp.1199-66, 2010.

P. V. Afonine, R. W. Grosse-kunstleve, N. Echols, and J. J. Headd,

N. W. Moriarty, M. Mustyakimov, T. C. Terwilliger, A. Urzhumtsev, P. H. Zwart et al., Towards Automated Crystallographic 1203 Structure Refinement with Phenix, Refine. Acta Crystallogr., Sect, vol.68, pp.352-364, 1202.

E. Chovancova, A. Pavelka, P. Benes, O. Strnad, J. Brezovsky et al., , 1206.

, PLoS Comput. Biol, vol.8, 2012.

R. D. Finn, J. Clements, S. R. Eddy, . Hmmer-web, and . Server,

, Interactive Sequence Similarity Searching, Nucleic Acids Res, pp.1212-1241, 2011.

Y. Huang, B. Niu, Y. Gao, L. Fu, W. Li et al., A Web 1214 Server for Clustering and Comparing Biological Sequences. Bio-1215 informatics 2010, vol.26, pp.680-682

K. Katoh, K. Misawa, K. Kuma, and T. Miyata, MAFFT: A Novel 1217 Method for Rapid Multiple Sequence Alignment Based on Fast Fourier 1218 Transform, Nucleic Acids Res, vol.30, issue.14, pp.3059-3066, 2002.

S. Kumar, G. Stecher, M. Li, C. Knyaz, K. Tamura et al., Molecular Evolutionary Genetics Analysis across Computing Plat-1221 forms, Mol. Biol. Evol, vol.35, issue.6, pp.1547-1549, 1220.

A. M. Waterhouse, J. B. Procter, D. M. Martin, and M. Clamp,

G. J. Barton, Jalview Version 2-a Multiple Sequence Alignment Editor 1224 and Analysis Workbench, Bioinformatics, vol.25, issue.9, pp.1189-1191, 2009.