Assalamualaikum and hello!
today we learn about Protein Data Bank(PDB)..
Actually,even me myself don't know what it is all about T__T
It is important for Biomedical students like us to know about this thingy ^^)
First of all,let me introduce and give some information about PDB~
The
Protein Data Bank (
PDB) is a repository for the 3-D structural data of large biological molecules, such as
proteins and
nucleic acids. (See also
crystallographic database). The data, typically obtained by
X-ray crystallography or
NMR spectroscopy and submitted by
biologists and
biochemists from around the world, are freely accessible on the Internet via the websites of its member organisations (
PDBe,
PDBj, and
RCSB). The PDB is overseen by an organization called the
Worldwide Protein Data Bank, wwPDB.
The PDB is a key resource in areas of
structural biology, such as
structural genomics. Most major scientific journals, and some funding agencies, such as the
NIH in the
USA, now require scientists to submit their structure data to the PDB. If the contents of the PDB are thought of as primary data, then there are hundreds of derived (i.e., secondary) databases that categorize the data differently. For example, both
SCOP and
CATH categorize structures according to type of structure and assumed evolutionary relations;
GO categorize structures based on genes.
HISTORY OF PDB
The PDB originated as a grassroots effort.
[1] In 1971, Walter Hamilton of the
Brookhaven National Laboratory agreed to set up the data bank at Brookhaven. Upon Hamilton's death in 1973, Tom Koeztle took over direction of the PDB. In January 1994,
Joel Sussman was appointed head of the PDB. In October 1998,
[2] the PDB was transferred to the
Research Collaboratory for Structural Bioinformatics (RCSB); the transfer was completed in June 1999. The new director was
Helen M. Berman of
Rutgers University (one of the member institutions of the RCSB).
[3] In 2003, with the formation of the wwPDB, the PDB became an international organization. The founding members are
PDBe (Europe), RCSB(USA), and
PDBj (Japan). The
BMRB joined in 2006. Each of the four members of
wwPDB can act as deposition, data processing and distribution centers for PDB data. The data processing refers to the fact that wwPDB staff review and annotates each submitted entry. The data are then automatically checked for plausibility. (The
source code for this validation software has been made available to the public at no charge.
SOME STRUCRURES OF PDB
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| Subtilisin |
1) Subtilisin
Subtilisin (serine endopeptidase) is a non-specific
protease (a
protein-digesting enzyme) initially obtained from
Bacillus subtilis.
Subtilisins belong to
subtilases, a group of
serine proteases that initiate the
nucleophilic attack on the
peptide (amide) bond through a serine
residue at the
active site. They are physically and chemically well-characterized enzymes. Subtilisins typically have molecular weights of about 20,000 to 45,000 dalton. They can be obtained from soil bacteria, for example,
Bacillus amyloliquefaciens. Subtilisins are secreted in large amounts from many
Bacillus species.
Subtilisins are widely used in commercial products, for example, in laundry
[2] and dishwashing detergents, cosmetics, food processing
[3], skin care ointments
[4], contact lens cleaners, and for research purposes in
synthetic organic chemistry.
The structure of subtilisin has been determined by
X-ray crystallography. It is a 275-residue
globular protein with several
alpha-helices, and a large
beta-sheet. It is structurally unrelated to the
chymotrypsin-clan of serine proteases, but uses the same type of
catalytic triad in the
active site. This makes it the classic example of
convergent evolution.
In molecular biology using
B. subtilis as a model organism, the gene encoding subtilisin (
aprE) is often the second gene of choice after
amyE for integrating reporter constructs into, due to its dispensability.
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| Prolyl aminopeptidase |
|
|
2) Prolyl aminopeptidase
The prolyl aminopeptidase complexes of Ala-TBODA [2-alanyl-5-tert-butyl-(1, 3, 4)-oxadiazole] and Sar-TBODA [2-sarcosyl-5-tert-butyl-(1, 3, 4)-oxadiazole] were analyzed by X-ray crystallography at 2.4 angstroms resolution. Frames of alanine and sarcosine residues were well superimposed on each other in the pyrrolidine ring of proline residue, suggesting that Ala and Sar are recognized as parts of this ring of proline residue by the presence of a hydrophobic proline pocket at the active site. Interestingly, there was an unusual extra space at the bottom of the hydrophobic pocket where proline residue is fixed in the prolyl aminopeptidase.
Moreover, 4-acetyloxyproline-betaNA (4-acetyloxyproline beta-naphthylamide) was a better substrate than Pro-betaNA. Computer docking simulation well supports the idea that the 4-acetyloxyl group of the substrate fitted into that space. Alanine scanning mutagenesis of Phe139, Tyr149, Tyr150, Phe236, and Cys271, consisting of the hydrophobic pocket, revealed that all of these five residues are involved significantly in the formation of the hydrophobic proline pocket for the substrate. Tyr149 and Cys271 may be important for the extra space and may orient the acetyl derivative of hydroxyproline to a preferable position for hydrolysis.
These findings imply that the efficient degradation of collagen fragment may be achieved through an acetylation process by the bacteria.
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| lexA repressor |
|
|
|
3) LexA repressor
Repressor LexA or
LexA is a
repressor enzyme (
EC 3.4.21.88) that represses
SOS response genes coding for
DNA polymerases required for repairing DNA damage. LexA is intimately linked to
RecA in the biochemical cycle of DNA damage and repair. RecA binds to DNA-bound LexA causing LexA to cleave itself in a process called
autoproteolysis.
DNA damage can be inflicted by the action of antibiotics. Bacteria require
topoisomerases such as
DNA gyrase or
topoisomerase IV for
DNA replication. Antibiotics such as
ciprofloxacin are able to prevent the action of these molecules by attaching themselves to the gyrase - DNA complex. This is counteracted by the polymerase repair molecules from the
SOS response. Unfortunately the action is partly counterproductive because ciprofloxacin is also involved in the synthetic pathway to
RecA type molecules which means that the bacteria responds to an antibiotic by starting to produce more repair proteins. These repair proteins can lead to eventual benevolent mutations which can render the bacteria resistant to ciprofloxacin.
Mutations are traditionally thought of as happening as a random process and as a liability to the organism. Many strategies exist in a cell to curb the rate of mutations. Mutations on the other hand can also be part of a survival strategy. For the bacteria under attack from an antibiotic, mutations help to develop the right biochemistry needed for defense. Certain polymerases in the SOS pathway are error-prone in their copying of DNA which leads to mutations. While these mutations are often lethal to the cell, they can also lead to mutations which improve the bacteria's survival. In the specific case of topoisomerases, some bacteria have mutated one of their amino acids so that the ciproflaxin can only create a weak bond to the topoisomerase. This is one of the methods that bacteria use to become
resistant to antibiotics.
Impaired LexA proteolysis has been shown to interfere with
ciprofloxacin resistance.
[1] This offers potential for
combination therapy that combine
quinolones with strategies aimed at interfering with the action of LexA either directly, or via RecA.
LINKS:
http://en.wikipedia.org/wiki/Subtilisin
http://en.wikipedia.org/wiki/Repressor_lexA
http://www.rcsb.org/pdb/explore/explore.do?structureId=1X2B
http://www.rcsb.org/pdb/results/results.do?outformat=&qrid=335D0850&tabtoshow=Current
