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. 1998 Aug;7(8):1661–1670. doi: 10.1002/pro.5560070801

All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly.

M Bergdoll 1, L D Eltis 1, A D Cameron 1, P Dumas 1, J T Bolin 1
PMCID: PMC2144073  PMID: 10082363

Abstract

The crystal structures of three proteins of diverse function and low sequence similarity were analyzed to evaluate structural and evolutionary relationships. The proteins include a bacterial bleomycin resistance protein, a bacterial extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as phylogenetic analyses, strongly indicate that the modern family of proteins represented by these structures arose through a rich evolutionary history that includes multiple gene duplication and fusion events. These events appear to be historically shared in some cases, but parallel and historically independent in others. A significant early event is proposed to be the establishment of metal-binding in an oligomeric ancestor prior to the first gene fusion. Variations in the spatial arrangements of homologous modules are observed that are consistent with the structural principles of three-dimensional domain swapping, but in the unusual context of the formation of larger monomers from smaller dimers or tetramers. The comparisons support a general mechanism for metalloprotein evolution that exploits the symmetry of a homooligomeric protein to originate a metal binding site and relies upon the relaxation of symmetry, as enabled by gene duplication, to establish and refine specific functions.

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Selected References

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  1. Adman E. T., Sieker L. C., Jensen L. H. Structure of a bacterial ferredoxin. J Biol Chem. 1973 Jun 10;248(11):3987–3996. [PubMed] [Google Scholar]
  2. Amor J. C., Harrison D. H., Kahn R. A., Ringe D. Structure of the human ADP-ribosylation factor 1 complexed with GDP. Nature. 1994 Dec 15;372(6507):704–708. doi: 10.1038/372704a0. [DOI] [PubMed] [Google Scholar]
  3. Asturias J. A., Eltis L. D., Prucha M., Timmis K. N. Analysis of three 2,3-dihydroxybiphenyl 1,2-dioxygenases found in Rhodococcus globerulus P6. Identification of a new family of extradiol dioxygenases. J Biol Chem. 1994 Mar 11;269(10):7807–7815. [PubMed] [Google Scholar]
  4. Bax B., Lapatto R., Nalini V., Driessen H., Lindley P. F., Mahadevan D., Blundell T. L., Slingsby C. X-ray analysis of beta B2-crystallin and evolution of oligomeric lens proteins. Nature. 1990 Oct 25;347(6295):776–780. doi: 10.1038/347776a0. [DOI] [PubMed] [Google Scholar]
  5. Beese L. S., Friedman J. M., Steitz T. A. Crystal structures of the Klenow fragment of DNA polymerase I complexed with deoxynucleoside triphosphate and pyrophosphate. Biochemistry. 1993 Dec 28;32(51):14095–14101. doi: 10.1021/bi00214a004. [DOI] [PubMed] [Google Scholar]
  6. Benjamin R. C., Voss J. A., Kunz D. A. Nucleotide sequence of xylE from the TOL pDK1 plasmid and structural comparison with isofunctional catechol-2,3-dioxygenase genes from TOL, pWW0 and NAH7. J Bacteriol. 1991 Apr;173(8):2724–2728. doi: 10.1128/jb.173.8.2724-2728.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bennett M. J., Choe S., Eisenberg D. Domain swapping: entangling alliances between proteins. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3127–3131. doi: 10.1073/pnas.91.8.3127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bennett M. J., Schlunegger M. P., Eisenberg D. 3D domain swapping: a mechanism for oligomer assembly. Protein Sci. 1995 Dec;4(12):2455–2468. doi: 10.1002/pro.5560041202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Benson D. A., Boguski M. S., Lipman D. J., Ostell J. GenBank. Nucleic Acids Res. 1997 Jan 1;25(1):1–6. doi: 10.1093/nar/25.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bernat B. A., Laughlin L. T., Armstrong R. N. Fosfomycin resistance protein (FosA) is a manganese metalloglutathione transferase related to glyoxalase I and the extradiol dioxygenases. Biochemistry. 1997 Mar 18;36(11):3050–3055. doi: 10.1021/bi963172a. [DOI] [PubMed] [Google Scholar]
  11. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  12. Candidus S., van Pée K. H., Lingens F. The catechol 2,3-dioxygenase gene of Rhodococcus rhodochrous CTM: nucleotide sequence, comparison with isofunctional dioxygenases and evidence for an active-site histidine. Microbiology. 1994 Feb;140(Pt 2):321–330. doi: 10.1099/13500872-140-2-321. [DOI] [PubMed] [Google Scholar]
  13. Drocourt D., Calmels T., Reynes J. P., Baron M., Tiraby G. Cassettes of the Streptoalloteichus hindustanus ble gene for transformation of lower and higher eukaryotes to phleomycin resistance. Nucleic Acids Res. 1990 Jul 11;18(13):4009–4009. doi: 10.1093/nar/18.13.4009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dumas P., Bergdoll M., Cagnon C., Masson J. M. Crystal structure and site-directed mutagenesis of a bleomycin resistance protein and their significance for drug sequestering. EMBO J. 1994 Jun 1;13(11):2483–2492. doi: 10.1002/j.1460-2075.1994.tb06535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eltis L. D., Bolin J. T. Evolutionary relationships among extradiol dioxygenases. J Bacteriol. 1996 Oct;178(20):5930–5937. doi: 10.1128/jb.178.20.5930-5937.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fukuyama K., Nagahara Y., Tsukihara T., Katsube Y., Hase T., Matsubara H. Tertiary structure of Bacillus thermoproteolyticus [4Fe-4S] ferredoxin. Evolutionary implications for bacterial ferredoxins. J Mol Biol. 1988 Jan 5;199(1):183–193. doi: 10.1016/0022-2836(88)90388-9. [DOI] [PubMed] [Google Scholar]
  17. Han S., Eltis L. D., Timmis K. N., Muchmore S. W., Bolin J. T. Crystal structure of the biphenyl-cleaving extradiol dioxygenase from a PCB-degrading pseudomonad. Science. 1995 Nov 10;270(5238):976–980. doi: 10.1126/science.270.5238.976. [DOI] [PubMed] [Google Scholar]
  18. Happe B., Eltis L. D., Poth H., Hedderich R., Timmis K. N. Characterization of 2,2',3-trihydroxybiphenyl dioxygenase, an extradiol dioxygenase from the dibenzofuran- and dibenzo-p-dioxin-degrading bacterium Sphingomonas sp. strain RW1. J Bacteriol. 1993 Nov;175(22):7313–7320. doi: 10.1128/jb.175.22.7313-7320.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Harayama S., Rekik M. Bacterial aromatic ring-cleavage enzymes are classified into two different gene families. J Biol Chem. 1989 Sep 15;264(26):15328–15333. [PubMed] [Google Scholar]
  20. Heiss G., Stolz A., Kuhm A. E., Müller C., Klein J., Altenbuchner J., Knackmuss H. J. Characterization of a 2,3-dihydroxybiphenyl dioxygenase from the naphthalenesulfonate-degrading bacterium strain BN6. J Bacteriol. 1995 Oct;177(20):5865–5871. doi: 10.1128/jb.177.20.5865-5871.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hofer B., Eltis L. D., Dowling D. N., Timmis K. N. Genetic analysis of a Pseudomonas locus encoding a pathway for biphenyl/polychlorinated biphenyl degradation. Gene. 1993 Aug 16;130(1):47–55. doi: 10.1016/0378-1119(93)90345-4. [DOI] [PubMed] [Google Scholar]
  22. Holm L., Sander C. The FSSP database of structurally aligned protein fold families. Nucleic Acids Res. 1994 Sep;22(17):3600–3609. [PMC free article] [PubMed] [Google Scholar]
  23. Levitt M., Chothia C. Structural patterns in globular proteins. Nature. 1976 Jun 17;261(5561):552–558. doi: 10.1038/261552a0. [DOI] [PubMed] [Google Scholar]
  24. Martín M. F., Liras P. Organization and expression of genes involved in the biosynthesis of antibiotics and other secondary metabolites. Annu Rev Microbiol. 1989;43:173–206. doi: 10.1146/annurev.mi.43.100189.001133. [DOI] [PubMed] [Google Scholar]
  25. Mazodier P., Cossart P., Giraud E., Gasser F. Completion of the nucleotide sequence of the central region of Tn5 confirms the presence of three resistance genes. Nucleic Acids Res. 1985 Jan 11;13(1):195–205. doi: 10.1093/nar/13.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nakai C., Kagamiyama H., Nozaki M., Nakazawa T., Inouye S., Ebina Y., Nakazawa A. Complete nucleotide sequence of the metapyrocatechase gene on the TOI plasmid of Pseudomonas putida mt-2. J Biol Chem. 1983 Mar 10;258(5):2923–2928. [PubMed] [Google Scholar]
  27. Navas J., León J., Arroyo M., García Lobo J. M. Nucleotide sequence and intracellular location of the product of the fosfomycin resistance gene from transposon Tn2921. Antimicrob Agents Chemother. 1990 Oct;34(10):2016–2018. doi: 10.1128/aac.34.10.2016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ohlendorf D. H., Lipscomb J. D., Weber P. C. Structure and assembly of protocatechuate 3,4-dioxygenase. Nature. 1988 Nov 24;336(6197):403–405. doi: 10.1038/336403a0. [DOI] [PubMed] [Google Scholar]
  29. Ohlendorf D. H., Orville A. M., Lipscomb J. D. Structure of protocatechuate 3,4-dioxygenase from Pseudomonas aeruginosa at 2.15 A resolution. J Mol Biol. 1994 Dec 16;244(5):586–608. doi: 10.1006/jmbi.1994.1754. [DOI] [PubMed] [Google Scholar]
  30. Ranganathan S., Walsh E. S., Godwin A. K., Tew K. D. Cloning and characterization of human colon glyoxalase-I. J Biol Chem. 1993 Mar 15;268(8):5661–5667. [PubMed] [Google Scholar]
  31. Roderick S. L., Matthews B. W. Structure of the cobalt-dependent methionine aminopeptidase from Escherichia coli: a new type of proteolytic enzyme. Biochemistry. 1993 Apr 20;32(15):3907–3912. doi: 10.1021/bi00066a009. [DOI] [PubMed] [Google Scholar]
  32. Sawaya M. R., Pelletier H., Kumar A., Wilson S. H., Kraut J. Crystal structure of rat DNA polymerase beta: evidence for a common polymerase mechanism. Science. 1994 Jun 24;264(5167):1930–1935. doi: 10.1126/science.7516581. [DOI] [PubMed] [Google Scholar]
  33. Schmitt E., Mechulam Y., Fromant M., Plateau P., Blanquet S. Crystal structure at 1.2 A resolution and active site mapping of Escherichia coli peptidyl-tRNA hydrolase. EMBO J. 1997 Aug 1;16(15):4760–4769. doi: 10.1093/emboj/16.15.4760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Senda T., Sugiyama K., Narita H., Yamamoto T., Kimbara K., Fukuda M., Sato M., Yano K., Mitsui Y. Three-dimensional structures of free form and two substrate complexes of an extradiol ring-cleavage type dioxygenase, the BphC enzyme from Pseudomonas sp. strain KKS102. J Mol Biol. 1996 Feb 9;255(5):735–752. doi: 10.1006/jmbi.1996.0060. [DOI] [PubMed] [Google Scholar]
  35. Shu L., Chiou Y. M., Orville A. M., Miller M. A., Lipscomb J. D., Que L., Jr X-ray absorption spectroscopic studies of the Fe(II) active site of catechol 2,3-dioxygenase. Implications for the extradiol cleavage mechanism. Biochemistry. 1995 May 23;34(20):6649–6659. doi: 10.1021/bi00020a010. [DOI] [PubMed] [Google Scholar]
  36. Taira K., Hayase N., Arimura N., Yamashita S., Miyazaki T., Furukawa K. Cloning and nucleotide sequence of the 2,3-dihydroxybiphenyl dioxygenase gene from the PCB-degrading strain of Pseudomonas paucimobilis Q1. Biochemistry. 1988 May 31;27(11):3990–3996. doi: 10.1021/bi00411a015. [DOI] [PubMed] [Google Scholar]
  37. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Volbeda A., Hol W. G. Pseudo 2-fold symmetry in the copper-binding domain of arthropodan haemocyanins. Possible implications for the evolution of oxygen transport proteins. J Mol Biol. 1989 Apr 5;206(3):531–546. doi: 10.1016/0022-2836(89)90499-3. [DOI] [PubMed] [Google Scholar]
  39. Yrjälä K., Paulin L., Kilpi S., Romantschuk M. Cloning of cmpE, a plasmid-borne catechol 2,3-dioxygenase-encoding gene from the aromatic- and chloroaromatic-degrading Pseudomonas sp. HV3. Gene. 1994 Jan 28;138(1-2):119–121. doi: 10.1016/0378-1119(94)90792-7. [DOI] [PubMed] [Google Scholar]
  40. Zilhao R., Courvalin P. Nucleotide sequence of the fosB gene conferring fosfomycin resistance in Staphylococcus epidermidis. FEMS Microbiol Lett. 1990 Mar 15;56(3):267–272. doi: 10.1016/s0378-1097(05)80052-7. [DOI] [PubMed] [Google Scholar]
  41. Zylstra G. J., Gibson D. T. Toluene degradation by Pseudomonas putida F1. Nucleotide sequence of the todC1C2BADE genes and their expression in Escherichia coli. J Biol Chem. 1989 Sep 5;264(25):14940–14946. [PubMed] [Google Scholar]

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