I need help with these three questions. you have read article and here is how yo
ID: 779547 • Letter: I
Question
I need help with these three questions. you have read article and here is how you can get the article. http://www.hindawi.com/journals/bmri/2012/156795/
here are the questions,
Case: Enolase
Questions:
(1) 1. Explain what is meant by %u201Chousekeeping%u201D gene and why the gene for enolase is not considered a housekeeping gene despite it being expressed in all tissues.
(2) 2. The authors characterize enolase as a %u201Cmoonlighting protein.%u201D Explain what this means and how it helps to explain the apparent paradox of finding enolase in organisms that do not use glycolysis for energy?
Explanation / Answer
(1) Explain what is meant by housekeeping gene ?
In molecular biology, Housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions.[Although some housekeeping genes (such as GAPDH, HSP90, and %u03B2-actin) are expressed at relatively constant levels in most non-pathological situations, other housekeeping genes may vary depending on experimental conditions
The origin of the term "housekeeping gene" remains obscure. Literature from 1976 used the term to describe specifically tRNA and rRNA.[5] Interpreting gene expression data can be problematic, with most human genes registering 5-10 copies per cell (possibly representing error). Housekeeping genes are expressed in at least 25 copies per cell and sometimes number in the thousands
why the gene for enolase is not considered a housekeeping gene?
Although it is expressed in most of the cells, the gene that encodes enolase is not considered a housekeeping gene since its expression varies according to the pathophysiological, metabolic, or developmental conditions of cells [11]. %u03B1-Enolase mRNA translation which is primarily under developmental control is significantly upregulated during cellular growth and practically undetectable during quiescent phases
(2) The authors characterize enolase as a moonlighting protein. Explain what this means ?
Implicit in the central dogma is the hypothesis that each protein gene product has but one function. However, over the past decade, it has become clear that many proteins have one or more unique functions, over-and-above the principal biological action of the specific protein. This phenomenon is now known as protein moonlighting and many well-known proteins such as metabolic enzymes and molecular chaperones are now recognised as moonlighting proteins. A growing number of bacterial species are being found to have moonlighting proteins and the moonlighting activities of such proteins can contribute to bacterial virulence behaviour. The glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPD) and enolase, and the cell stress proteins: chaperonin 60, Hsp70 and peptidyl prolyl isomerase, are among the most common of the bacterial moonlighting proteins which play a role in bacterial virulence. Moonlighting activities include adhesion and modulation of cell signalling processes. It is likely that only the tip of the bacterial moonlighting iceberg has been sighted and the next decade will bring with it many new discoveries of bacterial moonlighting proteins with a role in bacterial virulence
how enolase is found in organisms that do not use glycolysis for energy?
An enol is formed by the dehydration of 2-phosphoglycerate. Enolase catalyzes the formation of phosphoenolpyruvate (PEP).
(3) Druggability
Druggability is a term used in drug discovery to describe a biological target such as a protein that is known to or is predicted to bind with high affinity to a drug. Furthermore by definition, the binding of the drug to a druggable target must alter the function of the target with a therapeutic benefit to the patient. The concept of druggability is most often restricted to small molecules (low molecular weight organic substances) but also has been extended to include biologic medical products such as therapeutic monoclonal antibodies.
Drug discovery comprises a number of stages that lead from a biological hypothesis to an approved drug. Target identification is typically the starting point of the modern drug discovery process. Candidate targets may be selected based on a variety of experimental criteria. These criteria may include disease linkage (mutations in the protein are known to cause a disease), mechanistic rationale (for example, the protein is part of a regulatory pathway that is involved in the disease process), or genetic screens in model organisms. Disease relevance alone however is insufficient for a protein to become a drug target. In addition, the target must be druggable.