classification: understanding the diversity and principles of
DESCRIPTION
Classification: understanding the diversity and principles of. protein structure and function. MCSG 2001 structures. Protein structure classification. Main reference: Robert B. Russell (2002) Classification of Protein Folds. Molecular Biotechnology 20:17-28. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/1.jpg)
MCSG 2001 structures
protein structure and function
Classification: understanding the diversity and principles of
![Page 2: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/2.jpg)
Protein structure classification Main reference: Robert B. Russell (2002) Classification of Protein Folds. Molecular Biotechnology 20:17-28. Importance: central to studies of protein structure, function, and evolution Philosophy: phyletic vs. phenetic Method: structure comparison + human knowledge
![Page 3: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/3.jpg)
Approaches Hierarchical Based on the types and arrangements of
secondary structures Unit (level): domain Domain assignment - structural vs. functional (fold or function
in isolation) - automated assignment methods
(structure vs. sequence)
![Page 4: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/4.jpg)
![Page 5: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/5.jpg)
Assignment of Class All or All (could be subjective) / ( unit) or + Other classes
![Page 6: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/6.jpg)
Subjective class assignment
![Page 7: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/7.jpg)
Assignment of Fold Defined by the number, type, and arrangement of SSEs Connectivity (e.g. circular permutation, scrambled proteins)
![Page 8: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/8.jpg)
N
C
AB
DC N
CA
B
DC
..A..B..C..D.. ..C..D..A..B..
Circular Permutation (CP)
![Page 9: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/9.jpg)
1nls (Concanavalin) 1led (Lectin)
N
C
N C
Circular permutation example
![Page 10: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/10.jpg)
N
CN
C
1au1a_ (Interferon-) 2occc_ (Cytochrome C oxidase)
Scrambled protein pairs
![Page 11: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/11.jpg)
Assignment of Superfamily Homologous even in the absence of
significant sequence similarity - certain level of structural similarity - unusual structural features - low but significant sequence similarity
from structural alignment - key active site residues - sequence similarity bridges Divergence vs. convergence
![Page 12: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/12.jpg)
Assignment of Family significant sequence similarity
![Page 13: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/13.jpg)
superfolds, superfamilies, supersites TIM barrel, Rossmann-like, ferredoxin-like, b-propellers, 4-helix bundle, Ig-like, b-jelly rolls, Oligonucleotide/oligosaccharride binding (OB) fold, SH3-like. Structure -> function (only 50% correct)
![Page 14: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/14.jpg)
Structure implicates function?
![Page 15: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/15.jpg)
Classification databases SCOP - careful assignment of evolutionary relationships; homologous vs. analogous CATH - A:architecture FSSP - a list of structural neighbors VAST - NCBI’s Entrez
![Page 16: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/16.jpg)
![Page 17: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/17.jpg)
![Page 18: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/18.jpg)
CATH
![Page 19: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/19.jpg)
Common Folds
![Page 20: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/20.jpg)
Unique Folds
![Page 21: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/21.jpg)
Structure Comparison
• Evolutionary relationship• Structure classification
Growth factorCytokine
![Page 22: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/22.jpg)
Shapiro & Harris, 2000
9% sequence identity
![Page 23: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/23.jpg)
![Page 24: Classification: understanding the diversity and principles of](https://reader036.vdocuments.us/reader036/viewer/2022062502/56814a4a550346895db767c6/html5/thumbnails/24.jpg)
Structure Comparison Tools DALI ( http://www2.ebi.ac.uk/dali/ ) CE ( http://cl.sdsc.edu/ ) VAST (http://www.ncbi.nlm.nih.gov/Structure/VAST/vast.html
) Prosup ( http://www.came.sbg.ac.at ) FLASH (http://thr.ibms.sinica.edu.tw/flash/)