Navigation Links
Sulfurous ping-pong in the urinary tract
Date:12/18/2008

Transfer of information is a basic property of biological systems. Common examples include transfer of genetic information or nerve impulses.

Transmission of signals occurs at an even more fundamental level between and within cells, including signaling molecules, which bear a phosphate or a sulfate group. The latter contain a sulfur atom. Since these processes are of supreme importance, they have been extensively studied and a number of mechanisms and related protein structures have been revealed. Thus, it is even more surprising that ETH Zurich researchers studying transfer processes among sulfurylated molecules discovered a protein, sulfotransferase, whose function is known but which exhibits a previously unknown structure. The group of Rudi Glockshuber recently published a paper about the protein, called ASST, in the scientific journal PNAS.

ETH Zurich researchers crossed the disulfide bridge

The discovery of the signal transfer mechanism happened accidentally, as is often the case in scientific research. The Glockshuber group studies protein folding mechanisms, where bonds between two sulfur atoms in a protein chain, disulfide bridges, play an important role. While examining gene data banks, the researchers stumbled upon an unusual gene combination present in strains of E. coli which cause urinary tract infections: two genes for the disulfide bond formation machinery were clustered with the gene for ASST.

Since bacteria often contain functionally-related genes close to each other, the researchers decided to use ASST to study disulfide bond formation.

Hence, they decided to elucidate the structure of ASST. This turned out to be a tantalizing task because this protein is large and present in only minute amounts in a bacterial compartment called periplasm. By growing large-scale bacterial cultures the scientists could obtain sufficient material for crystallographic studies. The crystals of ASST were analyzed at the Swiss Light Source at Paul Scherrer Institut in Villigen, Switzerland.

Two propellers building a cage

This analysis, down to 2 ngstrm resolution, revealed that ASST indeed contains an extremely short disulfide bond which can presumably only be formed by the action of the disulfide bond formation machinery genetically associated with ASST. This disulfide bridge is a prerequisite for proper folding of this protein and could also play a role in regulating its catalytic activity.

However, these features were almost outweighed by other unusual discoveries: the researchers found a previously never-observed protein structure to catalyze this process. This structure consists of two equal propeller-like parts which contain active sites in the center of the two propellers, built of beta-pleated sheets. Such a structure has never been observed for a sulfotransferase.

How does this two-propeller machine function? To answer this question, the scientists replaced individual amino acids, i.e. building blocks of the protein. In addition, they used molecules acting as sulfuryl-donors and repeated crystallographic analyses. Now they saw that five amino acids containing nitrogen are essential for the function of ASST. They built a reaction cage that accommodates both the donor and the acceptor of the sulfuryl group. Furthermore, during the transfer, the sulfuryl group is directly, covalently bound to a histidine side chain of ASST. Thus, the signal is first transferred from the donor to ASST and subsequently from ASST to the acceptor. Such a ping-pong mechanism is unique in the processes of sulfuryl transfer.

Point of vantage against the bad" E. coli strains

A new structure, a new mechanism this opens up medically relevant perspectives. Goran Malojčić; the first author of this study, explains several interesting points. Since ASST is not present in mammals, the protein could be a feasible target for antibacterial drugs. Furthermore, since ASST is present exclusively in E. coli strains causing urinary tract infections, a selective action against these bacteria would leave the other, useful bacteria intact.

In addition, Malojčić intends to collaborate with in-silico chemists, who use computers to design molecules, and develop inhibitors of ASST. He also plans to use ASST for the synthesis of novel molecules bearing sulfuryl groups.


'/>"/>

Contact: Prof. Rudi Glockshuber
rudi@mol.biol.ethz.ch
41-446-332-351
ETH Zurich/Swiss Federal Institute of Technology
Source:Eurekalert

Related biology news :

1. Bacteria that cause urinary tract infections invade bladder cells
2. Cell transplants may improve severe urinary incontinence
3. UCLA/VA partners with ASU to advance biosensor technology for urinary tract infections
4. Scientists find facial scars increase attractiveness
5. BIO-key(R) Awarded PocketCop(R) Contracts From Major Law Enforcement Agencies
6. L-1 Identity Solutions Selected by the State of New York as the Winning Bidder to Provide Enrollment Services for a Contract Estimated at Up to $250 Million
7. SAIC Awarded $37 Million Contract to Support U.S. Army Program Executive Office - Enterprise Information Systems
8. Evolved Machines Selected as a Prime Contractor for DARPA Program to Engineer an Artificial Olfaction System
9. Alzheimers disease research attracts first partner
10. American College of Medical Genetics receives $13.5M NIH contract
11. What is wild? Odor attraction among different wildtype Drosophila
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2016)... Minn. , Jan. 20, 2016   MedNet ... supports the entire spectrum of clinical research, is pleased ... 2015. MedNet,s significant achievements are the result of the ... iMedNet eClinical , it,s comprehensive, easy-to-use ... --> --> Key MedNet growth achievements ...
(Date:1/13/2016)... --> --> ... report titled - Biometric Sensors Market - Global Industry Analysis, ... to the report, the global biometric sensors market was valued at ... US$1,625.8 mn by 2023, expanding at a CAGR of ... the biometric sensors market is expected to reach 1,799.6 ...
(Date:1/8/2016)... MANCHESTER, United Kingdom , Jan. 8, 2016   ... diagnostic products, today announced the closing of a $9 million ... Proceeds from the financing will be used to accelerate the ... for detecting early-stage pressure ulcers. United ... receiving CE Mark approval. The device,s introduction has been met ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... 9, 2016 DelveInsight,s, ... report provides in depth insights on the ... the Protein-Tyrosine Phosphatase 1B (PTP1B) Inhibitors. The ... various stages of development including Discovery, Pre-clinical, ... and Preregistration. Report covers the product clinical ...
(Date:2/8/2016)... 8, 2016 Should antibiotic bone cement products ... to prevent infection after standard total hip or knee ... ECRI Institute have been fielding a lot lately. ... Bottom Line?" --> "Antibiotic Bone ... --> While there isn,t a simple ...
(Date:2/8/2016)... 2016 --> ... innovation-driven oncology company developing next generation cancer therapeutics ... announced that chairman emeritus of Tata Sons Limited, ... company as part of the first close of ... Navam Capital and Aarin Capital. http://photos.prnewswire.com/prnh/20150923/766442 ...
(Date:2/8/2016)... ... February 08, 2016 , ... Thomas J. Todorow has joined ... President for Corporate Services and the Chief Financial Officer at The Children’s Hospital ... Treasury, Managed Care Contracting, Supply Chain, and Investments. , Prior to joining CHOP ...
Breaking Biology Technology: