Navigation Links
2 in 1: Multi-tasking protein provides new approaches for anti-tuberculosis drugs

In a paper published today in PNAS, scientists from the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, reveal new insights into the workings of enzymes from a group of bacteria including Mycobacterium tuberculosis, the bacterium that causes tuberculosis. The new findings present possible new opportunities for developing organism-specific drugs, which target the pathogen but leave other microorganisms, which are beneficial to us, untouched.

Tuberculosis remains one of the largest threats to human health worldwide, and one of the most frequent causes of death in HIV patients. With the increasing emergence of strains of Mycobacterium tuberculosis that are hyper-resistant to drugs, it becomes ever more urgent that novel treatments be developed, and the search for novel strategies for drug development is an important step in this process.

In the current study, Matthias Wilmanns and his group at EMBL identified a multi-tasking enzyme from Mycobacterium tuberculosis that catalyses reactions on two different molecules, or substrates. In most organisms, cells need two specific enzymes, known as HisA and TrpF, in order to produce two essential amino acids histidine and tryptophan. However, in Mycobacterium tuberculosis, the encoding gene for TrpF is missing, and the two reactions are instead catalysed by a single enzyme, which is able to recognize and bind to two different substrates. This enzyme is known as PriA.

Using the Mycobacterium tuberculosis version of the PriA enzyme as a model, the researchers were able to unravel the hitherto unknown mechanism of bi-substrate specific binding observed in this group of bacteria.

"When we solved the three-dimensional structure of PriA, we found that it has the unique ability to form two different substrate-specific active sites," Wilmanns says: "it can form a reaction-specific active site, or undergo what we call 'substrate-induced metamorphosis' to form a different active site."

To further verify these observations, Wilmanns and colleagues screened 20,000 small molecule compounds, and identified a handful which inhibited both PriA-catalysed reactions but had no effect on TrpF activity.

"We believe that this ability for bi-substrate catalysis in Mycobacterium tuberculosis could be a new opportunity for future drug development," Wilmanns concludes: "This organism-specific reaction process could be exploited, since only the pathogen but none of the other bacteria living in or on humans, many of which are important for our well being, would be targeted."


Contact: Sonia Furtado
European Molecular Biology Laboratory

Related biology news :

1. Blood-clotting protein linked to cancer and septicemia
2. A protein reinforces memory and prevents forgetfulness
3. Pitt team grows arteries with most elastic protein reported, big step for living vascular grafts
4. Scientists link protein to the insulation of the nervous systems wiring
5. New method for rapidly producing protein-polymers
6. New study shows soy protein lowers non-HDL cholesterol significantly more than milk protein
7. New method takes snapshots of proteins as they fold
8. Mayo researchers describe measles viral protein movement
9. Princeton scientists construct synthetic proteins that sustain life
10. Scripps Research chemist devises new method to quantify protein changes
11. Eating low-fat, thanks to lupin proteins
Post Your Comments:
(Date:5/3/2016)... , May 3, 2016  Neurotechnology, a provider ... MegaMatcher Automated Biometric Identification System (ABIS) , ... multi-biometric projects. MegaMatcher ABIS can process multiple complex ... any combination of fingerprint, face or iris biometrics. ... SDK and MegaMatcher Accelerator , which ...
(Date:4/19/2016)... , UAE, April 20, 2016 ... implemented as a compact web-based "all-in-one" system solution for ... biometric fingerprint reader or the door interface with integration ... modern access control systems. The minimal dimensions of the ... readers into the building installations offer considerable freedom of ...
(Date:3/31/2016)...   LegacyXChange, Inc. ... LegacyXChange is excited to release its first ... be launched online site for trading 100% guaranteed authentic ... also provide potential shareholders a sense of the value ... industry that is notorious for fraud. The video is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... WI (PRWEB) , ... June 23, 2016 , ... ... focused on quality, regulatory and technical consulting, provides a free webinar ... presented on July 13, 2016 at 12pm CT at no charge. , Incomplete ...
(Date:6/23/2016)... 2016  Amgen (NASDAQ: AMGN ) today ... life sciences incubator to accelerate the development of ... space at QB3@953 was created to help high-potential life ... many early stage organizations - access to laboratory infrastructure. ... launched two "Amgen Golden Ticket" awards, providing each winner ...
(Date:6/22/2016)... DIEGO , June 22, 2016 ... that will allow them to produce up to ... from one lot within one week. These high-quality, ... time laboriously preparing cells and spend more time ... possible through a proprietary, high-volume manufacturing process that ...
(Date:6/22/2016)... June 22, 2016  According to Kalorama Information, ... sequencing (NGS) market include significant efforts in automation ... More accessible and affordable sequencers, say the healthcare ... for consumables including sample prep materials.  The healthcare ... Sample Preparation for Next Generation Sequencing (NGS) , ...
Breaking Biology Technology: