Volume 119, Issue 3, Pages (September 2000)

Slides:

Advertisements

Similar presentations

Pancreatitis and Pancreatic Cancer David C WhitcombDavid C Whitcomb MD Ph.D. David C Whitcomb Professor of Medicine, Cell Biology & Physiology and Human.

Advertisements

Javed A. Khan, Ben M. Dunn, Liang Tong Structure

Volume 92, Issue 5, Pages (March 2007)

CYB561 homology modeling. CYB561 homology modeling.A, Close-up of mutation G88R in CYB561. The protein is shown in ribbon presentation in gray, the heme.

Volume 13, Issue 1, Pages (January 2005)

Volume 58, Issue 6, Pages (June 2015)

Prediction of IgE-binding epitopes by means of allergen surface comparison and correlation to cross-reactivity Fabio Dall'Antonia, PhD, Anna Gieras,

Grouping of Multiple-Lentigines/LEOPARD and Noonan Syndromes on the PTPN11 Gene Maria Cristina Digilio, Emanuela Conti, Anna Sarkozy, Rita Mingarelli,

Volume 23, Issue 6, Pages (May 2018)

Volume 6, Issue 7, Pages (July 1998)

Volume 13, Issue 1, Pages (January 2005)

Volume 86, Issue 2, Pages (July 1996)

Volume 123, Issue 4, Pages (October 2002)

Volume 17, Issue 11, Pages (November 2009)

Volume 11, Issue 9, Pages (September 2003)

Aoi Nakano, Hajime Nakano, Sal LaForgia, Leena Pulkkinen, Jouni Uitto

An RNA-Binding Chameleon

Volume 34, Issue 4, Pages (May 2009)

Volume 16, Issue 10, Pages (October 2008)

Volume 21, Issue 5, Pages (May 2013)

Structure of the Angiopoietin-2 Receptor Binding Domain and Identification of Surfaces Involved in Tie2 Recognition William A. Barton, Dorothea Tzvetkova,

Disaccharide Digestion: Clinical and Molecular Aspects

Volume 117, Issue 3, Pages (September 1999)

Peter Ianakiev, Michael W

Volume 13, Issue 2, Pages (February 2005)

Volume 119, Issue 2, Pages (August 2000)

Solution and Crystal Structures of a Sugar Binding Site Mutant of Cyanovirin-N: No Evidence of Domain Swapping Elena Matei, William Furey, Angela M.

Cedric Badowski, Adelene Y. L

Volume 10, Issue 3, Pages (March 2003)

Structure of Bax Motoshi Suzuki, Richard J. Youle, Nico Tjandra Cell

Volume 17, Issue 3, Pages (March 2009)

Per M. Knappskog, Jacek Majewski, Avi Livneh, Per Torgeir E

Volume 124, Issue 5, Pages (March 2006)

Volume 90, Issue 1, Pages (July 1997)

Structural Basis for Protein Recognition by B30.2/SPRY Domains

Structure of the Tie2 RTK Domain

Volume 15, Issue 1, Pages 5-11 (January 2008)

Volume 7, Issue 4, Pages (October 1997)

Structure, Exchange Determinants, and Family-Wide Rab Specificity of the Tandem Helical Bundle and Vps9 Domains of Rabex-5 Anna Delprato, Eric Merithew,

Sadaf Naz, Chantal M. Giguere, David C. Kohrman, Kristina L

Human Elastase 1: Evidence for Expression in the Skin and the Identification of a Frequent Frameshift Polymorphism Ulvi Talas, John Dunlop, Sahera Khalaf,

Volume 23, Issue 6, Pages (May 2018)

Antonina Roll-Mecak, Chune Cao, Thomas E. Dever, Stephen K. Burley

Volume 91, Issue 7, Pages (December 1997)

Volume 6, Issue 1, Pages (July 2000)

ICAT Inhibits β-Catenin Binding to Tcf/Lef-Family Transcription Factors and the General Coactivator p300 Using Independent Structural Modules Danette.

Meigang Gu, Kanagalaghatta R. Rajashankar, Christopher D. Lima

Crystal Structure of Saccharopine Reductase from Magnaporthe grisea, an Enzyme of the α-Aminoadipate Pathway of Lysine Biosynthesis Eva Johansson, James.

Opitz G/BBB Syndrome in Xp22: Mutations in the MID1 Gene Cluster in the Carboxy- Terminal Domain Karin Gaudenz, Erich Roessler, Nandita Quaderi, Brunella.

Volume 14, Issue 4, Pages (April 2006)

Volume 121, Issue 6, Pages (December 2001)

Tertiary Structure of Destrin and Structural Similarity between Two Actin-Regulating Protein Families H Hatanaka, K Ogura, K Moriyama, S Ichikawa, I.

Volume 85, Issue 5, Pages (May 1996)

Volume 3, Issue 9, Pages (September 1995)

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 10, Issue 3, Pages (March 2003)

Bruce L. Zuraw, MD, Jack Herschbach, BA

The structure of ribosomal protein S7 at 1

The Crystal Structure of an Unusual Processivity Factor, Herpes Simplex Virus UL42, Bound to the C Terminus of Its Cognate Polymerase Harmon J Zuccola,

Volume 119, Issue 2, Pages (August 2000)

Structure of the EntB Multidomain Nonribosomal Peptide Synthetase and Functional Analysis of Its Interaction with the EntE Adenylation Domain Eric J.

Structure of CD94 Reveals a Novel C-Type Lectin Fold

Volume 9, Issue 3, Pages (March 2001)

Structural Basis of Proline-Proline Peptide Bond Specificity of the Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile Magdalena Schacherl,

Figure 2 Compound heterozygous mutations in ADAM22

Structure of the Histone Acetyltransferase Hat1

Volume 20, Issue 7, Pages (July 2012)

Wenzhe Ma, Chao Tang, Luhua Lai Biophysical Journal

Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility

Volume 95, Issue 2, Pages (October 1998)

Presentation transcript:

Volume 119, Issue 3, Pages 615-623 (September 2000) SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis Roland H. Pfützer, M.Michael Barmada, Andrew P.J. Brunskill, Robert Finch, P.Suzanne Hart, John Neoptolemos, William F. Furey, David C. Whitcomb Gastroenterology Volume 119, Issue 3, Pages 615-623 (September 2000) DOI: 10.1053/gast.2000.18017 Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 1 Comparison of human,40 porcine (data from Hecht et al.31), and rat41 (GenBank accession no. M27883) SPINK1/PSTI. Exons are based on comparison of human SPINK1 with draft DNA sequence from GenBank accession no. NM_003122. Obs var; observed variations in human protein sequence deduced from allele polymorphisms. Bold type shows the position of N34S variant (changes human sequence to porcine sequence22). Asterisk shows the “bait” lysine (K) in human and porcine, and arginine (R) in rat that projects into the specificity pocket of trypsin during trypsin inhibition. Note that the homology between human and porcine SPINK1 (PSTI) is 39 of 56 amino acids (71%, see peptides 1, 3, 4, 8, 9, 10, 11, 13, 14, 17, 21, 29, 32, 39, 42, 47, and 48), and human and rat SPINK1 (reported as rat PSTI -II41) is 36 of 56 amino acids (64%). Rat PSTI-I is monitor peptide. Gastroenterology 2000 119, 615-623DOI: (10.1053/gast.2000.18017) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 2 Cumulative incidence of chronic pancreatitis in patients with SPINK1 mutations vs. patients without SPINK1 mutations. All patients are also PRSS1 (cationic trypsinogen) mutation negative. The vertical line at age 20 indicates the cutoff used for contingency table analysis. At this point 21 of 24 (87.5%) SPINK1 N34S mutation carriers had already developed symptoms of pancreatitis as compared with 41 of 64 (64.1%) nonmutation carriers. Gastroenterology 2000 119, 615-623DOI: (10.1053/gast.2000.18017) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 3 Superposition of the porcine SPINK1 structure (blue) on the human (modified for chymotrypsin specificity) SPINK1 structure (red). The main chain is shown as a ribbon diagram, whereas selected side chains are shown in a ball and stick representation. The flipping of side chains is apparent by comparing residues 33 and 34 in the 2 structures. Also shown are the target residue for cleavage (41) and the mutation site at residue 55 (codon numbering). The image was created with the program RIBBONS.42 Gastroenterology 2000 119, 615-623DOI: (10.1053/gast.2000.18017) Copyright © 2000 American Gastroenterological Association Terms and Conditions

Fig. 4 Tentative model for the human trypsin (yellow) human SPINK1 (red) complex. The main chain is shown as a ribbon diagram and selected side chains are shown in a ball and stick representation. The orientation is similar to that in Figure 3. Note the proximity of the binding loop (N34-Y41) and P55 to the enzyme. Y41 (K41 in wild-type SPINK1) is shown penetrating the enzyme's specificity pocket. The image was created with the program RIBBONS.42 Gastroenterology 2000 119, 615-623DOI: (10.1053/gast.2000.18017) Copyright © 2000 American Gastroenterological Association Terms and Conditions