Editing Active site (section)

==In drug discovery==
Identification of active sites is crucial in the process of [[drug discovery]]. The 3-D structure of the enzyme is analysed to identify active site residues and design drugs which can fit into them. Proteolytic enzymes are targets for some drugs, such as protease inhibitors, which include drugs against AIDS and hypertension.<ref name="Schechter2005">{{Cite journal|vauthors=Schechter I|date=2005|title=Mapping of the active site of proteases in the 1960s and rational design of inhibitors/drugs in the 1990s|journal=Current Protein & Peptide Science|volume=6|issue=6|pages=501–512|doi=10.2174/138920305774933286|pmid=16381600}}
</ref> These protease inhibitors bind to an enzyme's active site and block interaction with natural substrates.<ref name="DeDecker2000">
{{Cite journal|vauthors=DeDecker BS|date=2000|title=Allosteric drugs: thinking outside the active-site box|journal=[[Chemistry & Biology]]|volume=7|issue=5|pages=103–107|doi=10.1016/S1074-5521(00)00115-0|pmid=10801477|doi-access=free}}</ref> An important factor in drug design is the strength of binding between the active site and an enzyme inhibitor.<ref name="Zuercher2008">{{Cite journal|vauthors=Zuercher M|date=2008|title=Structure-Based Drug Design: Exploring the Proper Filling of Apolar Pockets at Enzyme Active Sites|journal=[[Journal of Organic Chemistry]]|volume=73|issue=12|pages=4345–4361|doi=10.1021/jo800527n|pmid=18510366}}</ref> If the enzyme found in bacteria is significantly different from the human enzyme then an inhibitor can be designed against that particular bacterium without harming the human enzyme. If one kind of enzyme is only present in one kind of organism, its inhibitor can be used to specifically wipe them out.

Active sites can be mapped to aid the design of new drugs such as enzyme inhibitors. This involves the description of the size of an active site and the number and properties of sub-sites, such as details of the binding interaction.<ref name = Schechter2005/> Modern database technology called CPASS (Comparison of Protein Active Site Structures) however allows the comparison of active sites in more detail and the finding of structural similarity using software.<ref name="Powers2006">{{Cite journal|vauthors=Powers R|date=2006|title=Comparison of protein active site structures for functional annotation of proteins and drug design|journal=[[Proteins (journal)|Proteins]]|volume=65|issue=1|pages=124–135|doi=10.1002/prot.21092|pmid=16862592|s2cid=2527166|url=http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1000&context=chemistrypowers|url-access=subscription}}</ref>

===Application of enzyme inhibitors===
{| class="wikitable"
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!  !! Example !! Mechanism of action
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| '''Anti-bacterial agent''' || [[Penicillin]] || The bacterial [[cell wall]] is composed of [[peptidoglycan]]. During bacterial growth the present crosslinking of peptidoglycan fibre is broken, so new cell wall monomer can be integrated into the cell wall. Penicillin works by inhibiting the [[DD-Transpeptidase|transpeptidase]] which is essential for the formation of crosslinks, so the cell wall is weakened and will burst open due to [[turgor pressure]].
|-
| '''Anti-fungi agent''' || [[Azole]] || [[Ergosterol]] is a [[sterol]] that forms the cell surface membrane of the [[fungi]]. Azole can inhibit its biosynthesis by inhibiting the [[Lanosterol 14 alpha-demethylase]], so no new ergosterol is produced and harmful 14α-lanosterol is accumulated within the cell. Also, azole may generate [[reactive oxygen species]].
|-
| '''Anti-viral agent''' || [[Saquinavir]]|| HIV protease is needed to cleave Gag-Pol polyprotein into 3 individual proteins so they can function properly and start viral packaging process. HIV protease inhibitors like Saquinavir inhibit it so no new mature viral particle can be made.
|-
| '''Insecticides''' || [[Physostigmine]] || In the animal [[nervous system]], [[Acetylcholinesterase]] is required to break down the neurotransmitter [[acetylcholine]] into [[acetate]] and [[choline]]. [[Physostigmine]] binds to its active site and inhibits it, so impulse signal cannot be transmitted through nerves. This results in the death of insects as they lose control of muscle and heart function.
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| '''Herbicides''' || [[Cyclohexanedione]] || Cyclohexanedione targets the [[Acetyl-CoA carboxylase]] which is involved in the first step of fat synthesis: ATP-dependent [[carboxylation]] of [[acetyl-CoA]] to [[malonyl-CoA]]. Lipids are important in making up the cell membrane.
|}