Paetzel Lab Publications - by project

Proteolytic reactions related to Coronavirus reactions

SARS-CoV-2 main protease

Hydrolytic enzyme that utilize the serine-lysine catalytic dyad mechanism

Signal peptidase
Signal peptide peptidase
Birnavirus VP4 protease
UmuD protease and LexA protease
Unusual serine proteases
β-lactamases

Protein secretion and membrane protein assembly

β-barrel assembly machinery (Bam)
YidC
CsaA
DmsD
Membrane protein assembly

Cardiac proteins

Myosin binding protein
Troponin

Other projects

Viral proteins
Industrial Enzymes
Phospholipid synthesis enzymes
Bacterial surface proteins

Signal peptidase

Structural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus.
Alexander, A.N., Worrall, L.J., Hu, J., Vuckovic, M., Satishkumar, N., Poon, R., Sobhanifar, S., Rosell, F.I., Jenkins, J., Chiang, D.*, Mosimann, W.A., Chambers, H.F., Paetzel, M., Chatterjee, S.S., & Strynadka, N.C.J.
Nature 613, 375-382 (2023)
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The Endoplasmic Reticulum Signal Peptidase Complex.
Paetzel, M.
Encyclopedia of Cell Biology Second Edition, Oxford: Elsevier. vol. 1, p.716-731 (2023)
Bradshaw Ralph A., Hart Gerald W. and Stahl Philip D. (eds.)
ISBN: 9780128216248; DOI: 10.1016/B978-0-12-821618-7.00273-X
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Bacterial Signal Peptidases.
Paetzel, M.
Subcellular Biochemistry 92, 187-219 (2019)
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Structure and mechanism of Escherichia coli type I signal peptidase.
Paetzel, M.
BBA-Molecular Cell Research 1843, 1497-1508 (2014)
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Synthesis and characterization of the Arylomycin lipoglycopeptide antibiotics and the crystallographic analysis of their complex with signal peptidase.
Liu, J., Luo, C., Smith, P.A., Chin, J.K., Page, M.G., Paetzel, M. & Romesberg, F.E.
J. Am. Chem. Soc. 133, 17869-17877 (2011)
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Crystallographic analysis of bacterial signal peptidase in ternary complex with Arylomycin A₂ and a β-sultam inhibitor.
Luo, C., Roussel, P., Dreier, J., Page, M.G. & Paetzel, M.
Biochemistry 48, 8976-8984 (2009)
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Altered -3 substrate specificity of E. coli signal peptidase 1 mutants as revealed by screening a combinatorial peptide library.
Dogan Ekici, O., Karla, A., Paetzel, M., Lively, M.O., Pei, D. & Dalbey, R.E.
J. Biol. Chem.282, 417-425 (2007)
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The identification of residues that control signal peptidase cleavage fidelity and substrate specificity.
Karla, A., Lively, M., Paetzel, M. & Dalbey, R. E.
J. Biol. Chem. 280, 6731-6741 (2005)
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Crystallographic and biophysical analysis of a bacterial signal peptidase in complex with a lipopeptide-based inhibitor.
Paetzel, M., Goodall, J.J., Kania, M., Dalbey, R.E. & Page, M.G.P.
J. Biol. Chem. 279, 30781-30790 (2004)
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Signal peptidases.
Paetzel, M., Karla, A., Strynadka, N.C.J. & Dalbey, R.E.
Chemical Reviews 102, 4549-4580 (2002)
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Crystal structure of a bacterial signal peptidase apo-enzyme: IMPLICATIONS FOR SIGNAL PEPTIDE BINDING AND THE SER-LYS DYAD MECHANISM.
Paetzel, M., Dalbey, R.E. & Strynadka, N.C.J.
J. Biol. Chem. 277, 9512-9519 (2002)
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Bacterial type I signal peptidases.
Carlos J.L., Paetzel, M., Klenotic, P.A., Strynadka, N.C.J. & Dalbey, R.E.
The Enzymes 3rd EditionVol. 22, 27-55 (2001)
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The role of the membrane spanning domain of type I signal peptidase in cleavage site selection.
Carlos, J.L., Paetzel, M., Brubaker, G., Karla, A., Ashwell, C.M., Lively, M.O., Cao, G., Bullinger, P. & Dalbey, R.E. ,
J. Biol. Chem. 275 , 38813-38822 (2000)
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The structure and mechanism of bacterial type I signal peptidases: a novel antibiotic target.
Paetzel, M., Dalbey, R.E., & Strynadka, N.C.J.,
Pharmacology & Therapeutics 87, 27-49 (2000)
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Mutational evidence of transition state stabilization by serine 88 in Escherichia coli type I signal peptidase.
Carlos, J.L., Klenotic, P.A., Paetzel, M., Strynadka, N.C.J. & Dalbey, R.E.
Biochemistry 39, 7276-7283 (2000)
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The role of the conserved box E residues in the active site of the Escherichia coli type I signal peptidase.
Klenotic,P.A., Carlos, J.L., Samuelson, J.C., Schuenemann, T.A., Tschantz, W.R., Paetzel, M. Strynadka, N.C.J. & Dalbey, R.E.
J. Biol. Chem. 275, 6490-6498 (2000)
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Crystal structure of a bacterial signal peptidase in complex with a beta-lactam inhibitor.
Paetzel, M., Dalbey,R.E. & Strynadka, N.C.J.
Nature 396, 186-190 (1998)
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Phosphatidylethanolamine mediates insertion of the catalytic domain of leader peptidase in membranes.
van Klompenburg, W., Paetzel, M., de Jong, J.M., Dalbey, R.E., Demel, R.A., von Heijne, G. & de Kruijff, B.
Febs Letters 431, 75-79 (1998)
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Use of site-directed chemical modification to study an essential lysine in Escherichia coli leader peptidase.
Paetzel, M., Strynadka, N.C.J., Tschantz, W.R., Casareno, R., Bullinger, P.R. & Dalbey, R.E.
J. Biol. Chem. 272, 9994-10003 (1997)
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Crystallization of a soluble, catalytically active form of Escherichia coli leader peptidase.
Paetzel, M., Chernaia, M., Strynadka, N., Tschantz, W., Cao, G., Dalbey, R.E. & James, M.N.G.
PROTEINS:Structure, Function, and Genetics 23, 122-125 (1995)
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Characterization of a soluble, catalytically active form of Escherichia coli leader peptidase:
requirement of detergent or phospholipid for optimal activity.
Tschantz, W.R., Paetzel, M., Cao, G., Suciu, D., Inouye, M. & Dalbey, R.E. Biochemistry 34, 3935-3941 (1995)
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Signal peptide peptidase

Structure of signal peptide peptidase A with C-termini bound in the active sites: insights into specificity, self-processing and regulation.
Nam, S.E. & Paetzel, M.
Biochemistry 52, 8811-8822 (2013)
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Crystal structure of Bacillus subtilis signal peptide peptidase A.
Nam, S.E., Kim, A.C. & Paetzel, M.
J. Mol. Biol. 419, 347-358 (2012)
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The Escherichia coli signal peptide peptidase a is a serine-lysine protease with a lysine recruited to the non-conserved amino-terminal domain in the S49 protease family.
Wang, P., Shim, E., Cravatt, B., Jacobsen, R., Schoeniger, J., Kim, A.C., Paetzel, M. & Dalbey, R.E.
Biochemistry 47, 6361-6369 (2008)
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Crystal structure of a bacterial signal peptide peptidase.
Kim, A.C., Oliver, D.C. & Paetzel, M.
J. Mol. Biol. 376, 352-366 (2008)
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SARS-CoV-2 main protease

Kinetic comparison of all eleven viral polyprotein cleavage site processing events by SARS-CoV-2 Main Protease using a linked protein FRET platform.
Kenward C., Vuckovic M., Paetzel M. & Strynadka N.C.J.
J. Biol. Chem. 300, (2024)
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A novel class of broad-spectrum active-site-directed 3C-like protease inhibitors with nanomolar antiviral activity against highly immune-evasive SARS-CoV-2 Omicron subvariants.
Pérez-Vargas J., Worrall L.J., Olmstead A.D., Ton A.T., Lee J., Villanueva I., Thompson C.A.H., Dudek S., Ennis S., Smith J.R., Shapira T., Guzman J., Gang S., Ban F., Vuckovic M., Bielecki M., Kovacic S., Kenward C., Hong C.Y., Gordon D.G., Levett P.N., Krajden M., Leduc R., Boudreault P.L., Niikura M., Paetzel M., Young R.N., Cherkasov A., Strynadka N.C.J., & Jean F.
Emerging Microbes & Infections 12, 2246594 (17 pages) (2023)
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X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation.
Lee, J., Kenward, C., Worrall, L.J., Vuckovic, M., Gentile, F., Ton, A., Ng, M., Cherkasov, A., Strynadka, N.C.J. & Paetzel, M.
Nature Communications 13, 5196 (2022)
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Crystallographic structure of wild-type SARS-CoV-2 main protease acyl-enzyme intermediate with physiological C-terminal autoprocessing site.
Lee, J., Worrall, L.J., Vuckovic, M., Rosell, F.I., Gentile, F., Ton, A., Caveney, N.A., Ban, F., Cherkasov, A., Paetzel, M. & Strynadka, N.C.J.
Nature Communications 11, 5877 (2020)
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Birnavirus VP4 protease

Crystal structures of Yellowtail ascites virus VP4 protease: trapping an internal cleavage site trans acyl-enzyme complex in a native Ser/Lys dyad active site.
Chung, I.Y.W. & Paetzel, M.
J. Biol. Chem. 288, 13068-13081 (2013)
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Tellina virus 1 VP4 peptidase.
Chung, I.Y.W. & Paetzel, M.
Handbook of Proteolytic Enzymes 3nd Edition Elsevier Ltd. ISBN 978-0-12-382219-2 Chapter 780, pages: 3523-3527 (2012)
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Crystal structure of a viral protease intramolecular acyl-enzyme complex. Insights into cis-cleavage at the VP4/VP3 junction of Tellina birnavirus.
Chung, I.Y. & Paetzel, M.
J. Biol. Chem. 286, 12475-12482 (2011)
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Expression, purification and crystallization of VP4 protease from Tellina virus 1.
Chung, I.Y. & Paetzel, M.
Acta Crystallographica F 67, 157-160 (2011)
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Profiling the substrate specificity of viral protease VP4 by a FRET-based peptide library approach.
Ekici,O.D., Zhu,J., Chung,I.Y., Paetzel, M., Dalbey, R.E. & Pei, D.
Biochemistry 48, 5753-5759 (2009)
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Crystal structure of the VP4 protease from infectious pancreatic necrosis virus reveals the acyl-enzyme complex for an intermolecular self-cleavage reaction.
Lee, J., Feldman, A.R., Delmas, B. & Paetzel, M.
J. Biol. Chem. 282, 24928-24937 (2007)
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Purification, crystallization and preliminary X-ray analysis of truncated and mutant forms of VP4 protease from infectious pancreatic necrosis virus.
Lee, J., Feldman, A.R., Chiu, E., Chan, C., Kim, Y.N., Delmas, B. & Paetzel, M.
Acta Crystallographica F62, 1235-1238 (2006)
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Crystal structure of a novel viral protease with a serine / lysine catalytic dyad mechanism.
Feldman , A. R., Lee, J., Delmas, B. & Paetzel, M.
J. Mol. Biol. 358, 1378-1389 (2006)
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Expression, purification and crystallization of a birnavirus-encoded protease, VP4, from blotched snakehead virus (BSNV).
Lee, J., Feldman , A. R., Delmas, B. & Paetzel, M.
Acta Crystallographica F62, 353-356 (2006)
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UmuD protease and LexA protease

UmuD and UmuD' proteins.
Paetzel, M. & Woodgate R.
Handbook of Proteolytic Enzymes 3nd Edition Elsevier Ltd. ISBN 978-0-12-382219-2 Chapter 773, pages: 3487-3492 (2012)
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UmuD and UmuD' proteins.
Paetzel, M. & Woodgate R.
Handbook of Proteolytic Enzymes 2nd Edition Elsevier Ltd. ISBN 0-12-079610-4 Chapter 616, pages: 1976-1981 (2004)
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Crystal structure of LexA: A conformational switch for regulation of self-cleavage.
Luo, Y., Pfuetzner, R.A., Mosimann, S., Paetzel, M., Frey, E.A., Cherney, M., Kim, B., Little, J.W. & Strynadka, N.C.J.
Cell 106, 585-594 (2001)
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Common protein architecture and binding sites in proteases utilizing a Ser/Lys dyad mechanism.
Paetzel, M. & Strynadka, N.C.J.
Protein Science 8, 2533-2536 (1999)
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Unusual serine proteases

Unconventional Serine Proteases: variations on the catalytic Ser/His/Asp triad configuration.
Ekici, O.D. Paetzel, M. & Dalbey, R.E.
Protein Science 17, 2023-2037 (2008)
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Catalytic hydroxyl/amine dyads within serine proteases.
Paetzel, M. & Dalbey, R.E.
TIBS 22, 28-31 (1997)
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β-lactamases

β-barrel assembly machinery (Bam)

Expression and Purification of the Individual Bam Components BamB-E.
Aulakh, S., Kim, K.H. & Paetzel, M.
Methods Mol. Biol. 1329, 179-188 (2015)
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Outer membrane protein biosynthesis: transport and incorporation of OM proteins (in)to the OM bilayer.
Kim, K.H., Aulakh, S. & Paetzel, M.
Chapter in the book: Bacterial Membranes: Structural and Molecular Biology. Horizon Scientific Press (2013)
Edited by: Han Remaut and Remi Fronzes
ISBN: 978-1-908230-27-0
Publisher: Caister Academic Press
Publication Date: January 2014
Cover: hardback
Book website

The bacterial outer membrane β-barrel assembly machinery.
Kim, K.H., Aulakh, S. & Paetzel, M.
Protein Science 21, 751-768 (2012)
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Video

Crystal structure of the β-barrel assembly machinery BamCD complex.
Kim, K.H., Aulakh, S. & Paetzel, M.
J. Biol. Chem. 286, 39116-39121 (2011)
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Crystallographic analysis of the C-terminal domain of the Escherichia coli lipoprotein BamC.
Kim, K.H., Aulakh, S., Tan, W. & Paetzel, M.
Acta Crystallographica F 67, 1350-1358 (2011)
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Structural characterization of Escherichia coli BamE, a lipoprotein component of the β-barrel assembly machinery complex.
Kim, K.H., Kang, H.S., Okon, M., Escobar, E., McIntosh, L.P. & Paetzel, M.
Biochemistry 50, 1081-1090 (2011)
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Crystal structure of Escherichia coli BamB, a lipoprotein component of the β-barrel assembly machinery complex.
Kim, K.H. & Paetzel, M.
J. Mol. Biol. 406, 667-678 (2011)
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YidC

Crystal structure of the major periplasmic domain of the bacterial membrane protein assembly facilitator YidC.
Oliver, D.C. & Paetzel, M.
J. Biol. Chem. 283, 5208-5216 (2008)
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CsaA

Phage display and crystallographic analysis reveals potential substrate/binging site interactions in the protein secretion chaperone CsaA from Agrobacterium tumefaciens.
Feldman, A.R., Shapova, Y.A., Wu, S.S.T., Oliver, D.C., Heller, M., McIntosh, L.P., Scott, J.K. & Paetzel, M.
J. Mol. Biol. 379, 457-470 (2008)
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Crystallographic analysis of Bacillus subtilis CsaA.
Shapova, Y.A. & Paetzel, M.
Acta Crystallographica D63, 478-485 (2007)
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DmsD

¹H, ¹³C and ¹⁵N resonance assignments and peptide binding site chemical shift perturbation mapping for the Escherichia coli redox enzyme chaperone DmsD.
Stevens, C.M., Okon, M., McIntosh, L.P. & Paetzel, M.
Biomolecular NMR Assignments 7, 193-197 (2013)
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Purification of a Tat leader peptide by co-expression with its chaperone.
Stevens, C.M. & Paetzel, M.
Protein Expression and Purification 84, 167-172 (2012)
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Structural analysis of a monomeric form of the twin-arginine leader peptide binding chaperone Escherichia coli DmsD.
Stevens,C.M, Winstone,T.M.L., Turner,R.J. & Paetzel, M.
J. Mol. Biol. 389, 124-133 (2009)
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Identification of residues in DmsD for twin-arginine leader peptide binding, defined through random and bioinformatics-directed mutagenesis.
Chan, C.S., Winstone, T.M., Chang, L., Stevens, C.M., Workentine, M.L., Li, H., Wei, Y., Ondrechen, M.J., Paetzel, M. & Turner, R.J.
Biochemistry 47, 2749-2759 (2008)
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Membrane protein assembly

Membrane protein insertion in bacteria from a structural perspective.
Paetzel, M. & Dalbey, R. E.
Protein Movement Across Membranes, edited by Jerry Eichler, Eurika.com publishers (2005)
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Myosin Binding Protein

Structural Characterization of the C3 Domain of Cardiac Myosin Binding Protein-C and its Hypertrophic Cardiomyopathy-Related R502W Mutant.
Zhang, X.L., De, S., McIntosh, L.P., & Paetzel, M.
Biochemistry 53, 5332-5342 (2014)
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Troponin

Crystal structure of cardiac troponin C regulatory domain with bound Cd²⁺ reveals a closed conformation and unique ion coordination.
Zhang, X.L., Tibbits, G.F. & Paetzel, M.
Acta Crystallographica Section D Biological Crystallography D69, 722-734 (2013)
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Crystal structure of cardiac troponin C regulatory domain in complex with cadmium and deoxycholic acid reveals novel conformation.
Li, A.Y., Lee, J., Borek, D., Otwinowski, Z., Tibbits, G.F. & Paetzel, M.
J. Mol. Biol. 413, 699-711 (2011)
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Viral proteins

Novel avian influenza H7N3 strain outbreak, British Columbia.
Hirst, M., Astell, C. R., Griffith, M., Coughlin, S. M., Moksa, M., Zeng, T., Smailus, D. E., Holt, R. A., Jones, S., Marra, M. A., Petric, M., Krajden, M., Lawrence, D., Mak, A., Chow, R., Skowronski, D. M., Tweed, R. A., Goh, S., Brunham, R. C., Robinson, J., Bowes, V., Sojonky, K., Byrne, S. K., Li, Y., Kobasa, D., Booth, T. & Paetzel, M.
Emerging Infectious Diseases 10, 2192-2195 (2004)
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Industrial Enzymes

Structure of the catalytic domain of glucoamylase from Aspergillus niger.
Lee, J. & Paetzel, M.
Acta Crystallographica F 67, 188-192 (2011)
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Phospholipid synthesis enzymes

Crystal structure of a mammalian CTP: phosphocholine cytidylyltransferase catalytic domain reveals novel active site residues within a highly conserved nucleotidyl-transferase fold.
Lee, J., Johnson, J.E., Ding, Z., Paetzel, M. & Cornell, R.B.
J. Biol. Chem. 284, 33535-33548 (2009)
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Bacterial surface proteins

Characterization of AgfB from Salmonella enteritidis thin aggregative fimbriae.
White, A.P. Collinson, S.K., Banser, P.A, Gibson, D.L., Paetzel, M., Strynadka, N.C.J. & Kay, W.W.
J. Mol. Biol. 311, 735-749 (2001)
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