Structural Analysis of Two Enzymes Catalysing Reverse Metabolic Reactions Implies Common Ancestry

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2002 Jul 3

PMID 12093726

Citations 8

Authors

Olga Mayans

Andreas Ivens

L Johan Nissen

Kasper Kirschner

Matthias Wilmanns

Affiliations

Soon will be listed here.

Abstract

The crystal structure of the dimeric anthranilate phosphoribosyltransferase (AnPRT) reveals a new category of phosphoribosyltransferases, designated as class III. The active site of this enzyme is located within the flexible hinge region of its two-domain structure. The pyrophosphate moiety of phosphoribosylpyrophosphate is co-ordinated by a metal ion and is bound by two conserved loop regions within this hinge region. With the structure of AnPRT available, structural analysis of all enzymatic activities of the tryptophan biosynthesis pathway is complete, thereby connecting the evolution of its enzyme members to the general development of metabolic processes. Its structure reveals it to have the same fold, topology, active site location and type of association as class II nucleoside phosphorylases. At the level of sequences, this relationship is mirrored by 13 structurally invariant residues common to both enzyme families. Taken together, these data imply common ancestry of enzymes catalysing reverse biological processes--the ribosylation and deribosylation of metabolic pathway intermediates. These relationships establish new links for enzymes involved in nucleotide and amino acid metabolism.

Citing Articles

Structure, mechanism and inhibition of anthranilate phosphoribosyltransferase.

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Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance.

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References

Kinoshita K, Sadanami K, Kidera A, Go N . Structural motif of phosphate-binding site common to various protein superfamilies: all-against-all structural comparison of protein-mononucleotide complexes. Protein Eng. 1999; 12(1):11-4. DOI: 10.1093/protein/12.1.11. View

Kleywegt G, Jones T . Software for handling macromolecular envelopes. Acta Crystallogr D Biol Crystallogr. 1999; 55(Pt 4):941-4. DOI: 10.1107/s0907444999001031. View

Vonrhein C, Schulz G . Locating proper non-crystallographic symmetry in low-resolution electron-density maps with the program GETAX. Acta Crystallogr D Biol Crystallogr. 1999; 55(Pt 1):225-9. DOI: 10.1107/S0907444998007914. View

Perrakis A, Morris R, Lamzin V . Automated protein model building combined with iterative structure refinement. Nat Struct Biol. 1999; 6(5):458-63. DOI: 10.1038/8263. View

Phillips C, Ullman B, Brennan R, Hill C . Crystal structures of adenine phosphoribosyltransferase from Leishmania donovani. EMBO J. 1999; 18(13):3533-45. PMC: 1171432. DOI: 10.1093/emboj/18.13.3533. View

Knochel T, Ivens A, Hester G, Gonzalez A, Bauerle R, Wilmanns M . The crystal structure of anthranilate synthase from Sulfolobus solfataricus: functional implications. Proc Natl Acad Sci U S A. 1999; 96(17):9479-84. PMC: 22234. DOI: 10.1073/pnas.96.17.9479. View

Knight S . RSPS version 4.0: a semi-interactive vector-search program for solving heavy-atom derivatives. Acta Crystallogr D Biol Crystallogr. 2000; 56(Pt 1):42-7. DOI: 10.1107/s0907444999012913. View

Craig 3rd S, Eakin A . Purine phosphoribosyltransferases. J Biol Chem. 2000; 275(27):20231-4. DOI: 10.1074/jbc.R000002200. View

Lang D, Thoma R, STERNER R, Wilmanns M . Structural evidence for evolution of the beta/alpha barrel scaffold by gene duplication and fusion. Science. 2000; 289(5484):1546-50. DOI: 10.1126/science.289.5484.1546. View

10.

Smith D, Parish T, Stoker N, Bancroft G . Characterization of auxotrophic mutants of Mycobacterium tuberculosis and their potential as vaccine candidates. Infect Immun. 2001; 69(2):1142-50. PMC: 97996. DOI: 10.1128/IAI.69.2.1442-1150.2001. View

11.

Lohkamp B, Coggins J, Lapthorn A . Purification, crystallization and preliminary X-ray crystallographic analysis of ATP-phosphoribosyltransferase from Escherichia coli. Acta Crystallogr D Biol Crystallogr. 2001; 56(Pt 11):1488-91. DOI: 10.1107/s0907444900011306. View

12.

Morollo A, Eck M . Structure of the cooperative allosteric anthranilate synthase from Salmonella typhimurium. Nat Struct Biol. 2001; 8(3):243-7. DOI: 10.1038/84988. View

13.

Ivens A, Mayans O, Szadkowski H, Wilmanns M, Kirschner K . Purification, characterization and crystallization of thermostable anthranilate phosphoribosyltransferase from Sulfolobus solfataricus. Eur J Biochem. 2001; 268(8):2246-52. DOI: 10.1046/j.1432-1327.2001.02102.x. View

14.

Spraggon G, Kim C, Yee M, Yanofsky C, Mills S . The structures of anthranilate synthase of Serratia marcescens crystallized in the presence of (i) its substrates, chorismate and glutamine, and a product, glutamate, and (ii) its end-product inhibitor, L-tryptophan. Proc Natl Acad Sci U S A. 2001; 98(11):6021-6. PMC: 33415. DOI: 10.1073/pnas.111150298. View

15.

Gerlt J, Babbitt P . Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies. Annu Rev Biochem. 2001; 70:209-46. DOI: 10.1146/annurev.biochem.70.1.209. View

16.

Hocker B, Jurgens C, Wilmanns M, STERNER R . Stability, catalytic versatility and evolution of the (beta alpha)(8)-barrel fold. Curr Opin Biotechnol. 2001; 12(4):376-81. DOI: 10.1016/s0958-1669(00)00230-5. View

17.

Chaudhuri B, Lange S, MYERS R, Chittur S, Davisson V, Smith J . Crystal structure of imidazole glycerol phosphate synthase: a tunnel through a (beta/alpha)8 barrel joins two active sites. Structure. 2001; 9(10):987-97. View

18.

Hocker B, Wilmanns M, STERNER R . Divergent evolution of (betaalpha)8-barrel enzymes. Biol Chem. 2001; 382(9):1315-20. DOI: 10.1515/BC.2001.163. View

19.

Pugmire M, Ealick S . Structural analyses reveal two distinct families of nucleoside phosphorylases. Biochem J. 2001; 361(Pt 1):1-25. PMC: 1222293. DOI: 10.1042/0264-6021:3610001. View

20.

Sinha S, Smith J . The PRT protein family. Curr Opin Struct Biol. 2001; 11(6):733-9. DOI: 10.1016/s0959-440x(01)00274-3. View