Professional Documents
Culture Documents
Archiv e
ePaper
eBooks
Classifieds
Subscriptions
Mobile
Apps
Social
SEARCH
Home
News
Opinion Business
Sport
S&T
Features
Entertainment
Books
GO
FIFA 2014
Jun
Mo
Tu
2014
We
Th
Fr
Sa
Proteins purified, >90% - Gene to expression, purification Yeast, E.coli, insect, mammalian lifeome.com/
Ads by Google
R. PRASAD
SHARE PRINT T+
Su
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
RECENT ARTIC
Did Euge
A chatbot, n
13-year-old
test - makin
pdfcrowd.com
Ads by Googl e
HU plays a role in the expression of several genes (a few hundred genes). So it is called a global
regulator of gene expression, said Prof. Suryanarayanarao Ramakumar, Department of Physics, IISc,
Bangalore and a co-author of the paper.
Considering the predominant role played by the gene encoding for HU protein, knocking the gene
would in effect kill the TB causing bacterium Mycobacterium tuberculosis . And that was precisely
what the team ended up doing.
Since the HU protein binds to DNA and compacts it, they identified small molecules that can bind to
the surface of the HU protein and inhibit the binding.
In effect, the small molecules prevent HU-DNA interaction by binding to the protein. As a result, DNA
compaction is disrupted and gene expression goes haywire, explained Prof. Nagaraja. Since gene
expression is the hallmark of life, the small molecule causes the bacterias death.
Ads by Googl e
To identify the small molecules that can bind to the HU protein, the researchers first cloned the HUencoding gene. The protein that got expressed in large quantities was then purified. Prof. Ramakumars
team went ahead and derived the 3D structure of the protein using X-ray crystallography. The next
step involved the identification of the core of interaction in the HU protein. This was done for the first
time, said Prof. Ramakumar.
The DNA-binding protein has a large interface for interaction with the DNA. So in the large interface,
the researchers had to identify the core of interaction region the major part that interacts with the
DNA. Prof. Nagaraja likens the core of interaction to a cavity where something can go and fit in well.
Only one cavity which plays a role in the DNA binding was identified, said Prof. Nagaraja.
Following the identification of the core region, the researchers had to identify molecules that inhibit
the binding of HU protein with DNA. This was done using computational method. Two small (with
respect to proteins) chemical entities trans-stilbene derivatives were identified. Subsequently,
pdfcrowd.com
did further studies to confirm the inhibitory action of stilbene derivatives, explained Prof.
Ramakumar.
T he basis
ePaper
In the case of E. coli , there are 12 genes encoding for histone-like proteins that play a key role in DNA
compaction, and there are many genes that can act as a backup in case one gene is compromised.
Many of these genes in E. coli serve a redundant or backup function for HU. So HU protein is not
essential for cell survival in the case of E. coli , Prof. Nagaraja explained.
In contrast, in Mtb, only five histone-like proteins have been identified. But there seems to be no
additional gene that can do a function similar to that of HU protein. Hence, HU protein is vital for
Mtbs survival.
We realised that the under-representation of histone-like protein in Mtb means there is no backup for
the HU protein when it is knocked off. We realised the new approach to target the TB pathogen, Prof.
Nagaraja explained. Had a hunch wanted to study the HU protein in greater detail.
Quite surprisingly, while HU has been studied extensively in other organisms, it has not been studied
thoroughly in Mycobacterium tuberculosis the bacterium that causes TB.
GROUP SITES
The Hindu
Business Line
Sportstar
Frontline
Im ages
Classifieds
Miles to go
Prof. Nagaraja is extremely cautious of the new molecules clinical potential. This kind of basic
research opens up new approaches to intervention. But clearly more studies are required to take it to
the next level, he noted.
This is an important, breakthrough research, but there are caveats for translation [into clinical use].
We need better molecules and need to take it beyond the lab, he emphasised, snuffing out any false
hope of these molecules becoming the magic bullet to get rid of TB bacteria right away.
Inhibition [of binding] is inefficient The potency is not sufficient to go in for animal studies. Need to
find better molecules [there is] no way you can use these molecules directly but can aim to develop
better molecules.
In the end, its a proof-of-concept study, and a novel way of targeting TB bacteria. Thats the key
point, Prof. Nagaraja concluded.
pdfcrowd.com
Like
Share
19
Tweet
11 Jun 2014
21 Jun 2014
21 Jun 2014
Styleblazer
19 Jun 2014
NJ.com
26 Apr 2014
what's this?
Ads by Googl e
lifeome.com/
Email the Editor
pdfcrowd.com
The Hindu: Home | News | Opinion | Business | Sport | S & T | Feat ures | Ent ert ainment | Books | In School | In-dept h | Jobs | FIFA 2014 |
The Sit e: | About Us | Terms of Use | Privacy Policy | Cont act s | Archive | Subscript ion | RSS Feeds | Sit e Map
Group Sit es: The Hindu |
| Business Line | Sport st ar | Front line | The Hindu Cent re | The Hindu Hub |
Publicat ions | eBooks | Images | Classifieds |
pdfcrowd.com