Types of Organisms: Prokaryotic, Eukaryotic, and Archea
Protein Maturation
Deciphering a Swiss-Prot entry
Specialized protein databases: KEGG (the metabolic pathways database) or PDB (structure database)
2 ways to predict genetics
1. Genes to proteins or translation (genomics)
2. DNA
We must merge the two
From Gene to functional Protein
DNA > mRNA > proteins > upon maturing > transportation > destination
Protein Maturation:
-removal of some fragments
-specific protein cleavage
-chemical modifications
-Phosphorylation (addition of phosphate that gives the protein its shape)
-adition of lipids or sugars (glycosylation)
-Proteins are often modified to make them active
-Modification can imply attaching a lipid or a sugar
-Use these resources to determine the details of the modification
Swiss-Prot Database – (British) entries describe all proteins that have known functions
tremble contains the 4 mill putative proteins found in GenBank
Swiss-Prot contains the subset of tremble with a known function
This is redundant to create many databases using the same information
A Swiss-Prot entry: www.expasy.org/uniprot/P00533
Gen Info (accession number), References, Commments, Cross-reference, feature table, sequence
General Information: Entry Name, Primary Accession Number (PXXXX [P is for protein]), Last Modified, Protein name and synonyms, from/taxonomy fields (tells where protein came from), references section
Comments section lists all the known functions of the protein
Features Section localizes precisely every known function of your protein, each on its sequence
• TRANSMEM: Transmembrane domain (something that passes through the membrane)
• ACT_SITE: Active sites (where chemicals can bond)
• BINDING: Binding sites
• DISULPHID: Bridge of cysteines
• EMBL: GenBank original DNA sequence
• PDB: Experimental structure of your protein
• DIP: Proteins interacting with your protein
• GlycoSuiteDB: Glycolsylations
• MIM: List of genetic diseases involving your protein
• Ontologies: Function of your protein
• Profiles: Known protein domains in your protein
• ENSEMBL: Genomic location of your protein
By alternative splicing, the protein can have MANY functions
• To find out about the function of your protein, you will need to determine
– Where your protein works
– Metabolic pathway in which the protein is involved
– The protein's 3D structure
– Which protein family it belongs to
Where do proteins work?
Part of the metabolic pathway
Chain of production linking several different proteins
Modify metabolites by passing them from one enzyme to the next
On KEGG pathway, each enzyme appears w/its EC number
– KEGG is the most extensive database of metabolic pathways
– You can use it to compare species Japan
– The IUBMD assigns the EC numbers used to describe an enzyme activity UK
– An exhaustive list of all known metabolic pathways in E. coli and other bacteria
Some important Protein Families
– Kinases control everything in us; their deregulation is the cause of many cancers
– Immunoglobulins are key elements of our natural defenses
– This site is a key resource on restriction enzymes
Predicting protein function is a central goal in biology
• Protein databases help organize knowledge
• They provide the material for
– Developing new biological experiments
– Developing new prediction algorithms
– Extrapolating experimental data to unknown sequences
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