Andrew T. Russo, Mark A. White, Stanley J. Watowich  Structure 

Slides:



Advertisements
Similar presentations
Javed A. Khan, Ben M. Dunn, Liang Tong  Structure 
Advertisements

Volume 10, Issue 8, Pages (August 2002)
Volume 14, Issue 1, Pages (January 2006)
Crystal structure of the chemotaxis receptor methyltransferase CheR suggests a conserved structural motif for binding S-adenosylmethionine  Snezana Djordjevic,
Ross Alexander Robinson, Xin Lu, Edith Yvonne Jones, Christian Siebold 
Volume 10, Issue 8, Pages (August 2002)
Ping Wang, Katelyn A. Doxtader, Yunsun Nam  Molecular Cell 
Volume 20, Issue 6, Pages (June 2013)
Volume 87, Issue 2, Pages (October 1996)
Structure of an LDLR-RAP Complex Reveals a General Mode for Ligand Recognition by Lipoprotein Receptors  Carl Fisher, Natalia Beglova, Stephen C. Blacklow 
Volume 21, Issue 5, Pages (May 2013)
Volume 124, Issue 1, Pages (January 2006)
Volume 11, Issue 12, Pages (December 2003)
Chaperone-Assisted Crystallography with DARPins
Volume 93, Issue 4, Pages (May 1998)
Volume 16, Issue 10, Pages (October 2008)
Volume 10, Issue 12, Pages (December 2002)
Volume 23, Issue 7, Pages (July 2015)
Volume 14, Issue 3, Pages (March 2006)
Structure of the Angiopoietin-2 Receptor Binding Domain and Identification of Surfaces Involved in Tie2 Recognition  William A. Barton, Dorothea Tzvetkova,
Volume 21, Issue 6, Pages (June 2013)
Volume 14, Issue 5, Pages (May 2006)
Nadine Keller, Jiří Mareš, Oliver Zerbe, Markus G. Grütter  Structure 
Crystal Structure of the MHC Class I Homolog MIC-A, a γδ T Cell Ligand
Volume 13, Issue 4, Pages (April 2005)
Volume 31, Issue 2, Pages (July 2008)
Crystal Structure of Human CD38 Extracellular Domain
Ross Alexander Robinson, Xin Lu, Edith Yvonne Jones, Christian Siebold 
Volume 16, Issue 10, Pages (October 2008)
Volume 14, Issue 2, Pages (February 2006)
Volume 17, Issue 3, Pages (March 2009)
Crystal Structures of RNase H Bound to an RNA/DNA Hybrid: Substrate Specificity and Metal-Dependent Catalysis  Marcin Nowotny, Sergei A. Gaidamakov, Robert.
Structural Analysis of Ligand Stimulation of the Histidine Kinase NarX
The Monomeric dUTPase from Epstein-Barr Virus Mimics Trimeric dUTPases
Volume 124, Issue 5, Pages (March 2006)
Danny N.P Doan, Terje Dokland  Structure 
Structural Basis for Protein Recognition by B30.2/SPRY Domains
The Crystal Structure of the Costimulatory OX40-OX40L Complex
Volume 14, Issue 5, Pages (May 2006)
Volume 33, Issue 2, Pages (January 2009)
Volume 15, Issue 2, Pages (February 2007)
Structural Basis of EZH2 Recognition by EED
Volume 91, Issue 5, Pages (November 1997)
Crystal Structure of Human CD38 Extracellular Domain
Masaru Goto, Rie Omi, Noriko Nakagawa, Ikuko Miyahara, Ken Hirotsu 
Volume 15, Issue 2, Pages (February 2007)
Crystal Structures of the BAR-PH and PTB Domains of Human APPL1
Meigang Gu, Kanagalaghatta R. Rajashankar, Christopher D. Lima 
Tianjun Zhou, Liguang Sun, John Humphreys, Elizabeth J. Goldsmith 
Crystal Structures of Mycobacterium tuberculosis KasA Show Mode of Action within Cell Wall Biosynthesis and its Inhibition by Thiolactomycin  Sylvia R.
Crystal Structures of Mycobacterium tuberculosis KasA Show Mode of Action within Cell Wall Biosynthesis and its Inhibition by Thiolactomycin  Sylvia R.
Volume 15, Issue 3, Pages (March 2007)
Structure of the Staphylococcus aureus AgrA LytTR Domain Bound to DNA Reveals a Beta Fold with an Unusual Mode of Binding  David J. Sidote, Christopher.
Volume 17, Issue 7, Pages (July 2009)
Volume 14, Issue 6, Pages (June 2006)
Robert S. Magin, Glen P. Liszczak, Ronen Marmorstein  Structure 
Volume 91, Issue 5, Pages (November 1997)
Hideki Kusunoki, Ruby I MacDonald, Alfonso Mondragón  Structure 
Crystal Structures of RNase H Bound to an RNA/DNA Hybrid: Substrate Specificity and Metal-Dependent Catalysis  Marcin Nowotny, Sergei A. Gaidamakov, Robert.
Crystal Structure of the Tyrosine Phosphatase SHP-2
Volume 13, Issue 5, Pages (May 2005)
Structural Basis of Proline-Proline Peptide Bond Specificity of the Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile  Magdalena Schacherl,
Volume 127, Issue 7, Pages (December 2006)
The Structure of Sortase B, a Cysteine Transpeptidase that Tethers Surface Protein to the Staphylococcus aureus Cell Wall  Yinong Zong, Sarkis K Mazmanian,
The Structure of T. aquaticus DNA Polymerase III Is Distinct from Eukaryotic Replicative DNA Polymerases  Scott Bailey, Richard A. Wing, Thomas A. Steitz 
Structure of GABARAP in Two Conformations
Volume 13, Issue 4, Pages (April 2005)
Robert S. Magin, Glen P. Liszczak, Ronen Marmorstein  Structure 
Volume 95, Issue 2, Pages (October 1998)
Volume 14, Issue 8, Pages (August 2006)
Presentation transcript:

The Crystal Structure of the Venezuelan Equine Encephalitis Alphavirus nsP2 Protease  Andrew T. Russo, Mark A. White, Stanley J. Watowich  Structure  Volume 14, Issue 9, Pages 1449-1458 (September 2006) DOI: 10.1016/j.str.2006.07.010 Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 1 Sequence Alignment of nsP2pro from Representative Alphaviruses Active site residues are highlighted in green and are marked with a star below the alignment. The nsP2/3 cleavage site residues (Glu-Ala-Gly-Cys) are indicated by a green bar above the alignment. Secondary structure annotation, based on the VEEV structure, is indicated above the alignment. Sequences used in this alignment are: VEEV (Venezuelan equine encephalitis virus; Kinney et al., 1989), Aura (Aura virus; Rumenapf et al., 1995), WEEV (Western equine encephalitis virus 5614; Uryvaev et al., 1994), BFV (Barmah Forest virus; Lee et al., 1997), ONNV (O'nyong-nyong virus SG650; Lanciotti et al., 1998), RRV (Ross River virus NB5092; Faragher et al., 1988), SFV (Semliki Forest virus; Salonen et al., 2003), and SINV (Sindbis virus MRE16; Myles et al., 2003). Sequences were aligned with Megalign (DNASTAR, Inc.). The figure was prepared with ESPript (Gouet et al., 1999). Structure 2006 14, 1449-1458DOI: (10.1016/j.str.2006.07.010) Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 2 Structure of VEEV nsP2pro (A) Trace of nsP2pro Cα atoms colored from blue (N terminus) to red (C terminus) with every 10th residue displayed as a light-gray ball. Every 20th residue position is labeled. (B) Ribbon diagram of nsP2pro colored from blue (N terminus) to red (C terminus) and including bound water (red spheres). (C) B factor “worm” representation of nsP2pro. Color and tube diameter reflect relative main chain B factors. Red color and a large diameter indicate high B values. The catalytic residues Cys477 and His547 are shown in ball-and-stick, and waters are shown as red spheres. All wall-eye stereographic images were made with Pymol. Structure 2006 14, 1449-1458DOI: (10.1016/j.str.2006.07.010) Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 3 Superposition of the nsP2pro Catalytic Dyad with Those of Papain and Human Cathepsin X (A) A close-up view of the catalytic dyad of cathepsin X (green) and papain (red) showing strong similarity between the two and clear structural differences from VEEV nsP2pro (light blue). The divergence of nsP2pro from the papain and cathepsin X structures increases with increasing distance from catalytic dyad. (B) An expanded view of the superposition of cysteine protease structures shows that cathepsin X (green) and papain (red) have similar two-domain tertiary structures, and that they form distinct tertiary structures relative to VEEV nsP2pro (light blue). Structure 2006 14, 1449-1458DOI: (10.1016/j.str.2006.07.010) Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 4 Model of the EAGA Peptide Bound at the nsP2pro Active Site (A) Surface rendering of nsP2pro and a stick model of the EAGA substrate. The N-terminal domain is colored pale blue, and the C-terminal domain is colored tan. The catalytic residues plus Trp547 are colored by atom type, with carbon colored magenta, nitrogen colored blue, oxygen colored red, and sulfur colored yellow. The peptide substrate is colored similarly by atom type, except that carbon atoms are green. (B) Close-up view of the nsP2pro substrate binding groove with the model EAGA consensus substrate bound. Atom coloring is as in Figure 3A. Placement of the substrate peptide clearly indicates the S1, S2, and S3 substrate binding sites. (C) Close-up view of the residues in the nsP2pro binding groove and the bound substrate. Structure 2006 14, 1449-1458DOI: (10.1016/j.str.2006.07.010) Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 5 Superposition of the nsP2 C-Terminal Domain with E. coli FtsJ RNA Methyltransferase FtsJ methyltransferase is shown in green, and the C-terminal domain of VEEV nsP2pro is colored tan. SAM substrate bound to FtsJ is colored light blue. Superposition was obtained by maximizing the spatial overlap of the six longest β strands in the core region of each protein. Although the core β sheets are conserved, the remaining secondary structural elements are not. The secondary structure surrounding the SAM binding site is not conserved, indicating that this domain in nsP2pro is likely not a functional methyltransferase. Structure 2006 14, 1449-1458DOI: (10.1016/j.str.2006.07.010) Copyright © 2006 Elsevier Ltd Terms and Conditions

Figure 6 Locations of Temperature-Sensitive Mutants Mapped onto the VEEV nsP2pro Structure The nsP2pro cartoon is colored by domain as in Figure 2. Stick representations of residues are colored by atom type, with carbon atoms in the mutation sites (labeled) colored green and the catalytic dyad (unlabeled) colored magenta. Structure 2006 14, 1449-1458DOI: (10.1016/j.str.2006.07.010) Copyright © 2006 Elsevier Ltd Terms and Conditions