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[[Image:Tryptophan Synthase Dimer 3.png|250px|left|thumb| ]] | [[Image:Tryptophan Synthase Dimer 3.png|250px|left|thumb| ]] | ||
=Tryptophan Synthase= | |||
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Tryptophan | Tryptophan Synthase is an ideal model for illustrating the complex protein-protein interactions that occur between biomolecules. Each subunit communicates with the other cooperatively to maximize the catalytic rate of the synthesis of L-tryptophan from indole-3-glycerol-phosphate. The overall synthesis is completed by the substrate binding to the active site in the a-subunit, the product then channeled to the b-subunit active site, and then the product released. | ||
__TOC__ | __TOC__ | ||
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==Enzyme Structure== | ==Enzyme Structure== | ||
Tryptophan synthase typically exists as an α-ββ-α complex. The α subunit has an α/β barrel, which is formed from eight parallel beta strands with eight parallel α-helicies packed around it.The β-subunit consists of two domains called the N-terminal domain and C-terminal domain.<ref name="cite7">http://tryptophan.net/Trpsynthase/Tryptophan%20Synthase.html</ref> | |||
===Hydrophobic Channel=== | |||
The α and β active sites are separated by a 30 Å long hydrophobic channel contained within the enzyme allowing for the diffusion of indole. If the channel did not exist, the indole formed at an α active site would quickly diffuse away and be lost to the cell as it is hydrophobic and can easily cross membranes. As such, the channel is essential for enzyme complex function<ref name="cite6">http://www.annualreviews.org/doi/abs/10.1146/annurev.biochem.70.1.149</ref> | |||
---- | ---- | ||
===Sequence of TrpA and Trp B=== | |||
'''Alpha Subunit''' | '''Alpha Subunit''' | ||
[[Image:Chain.jpg.png| | [[Image:Chain.jpg.png|400px|]] | ||
'''Beta Subunit''' | '''Beta Subunit''' | ||
[[Image:Chain.jpg-2.png| | [[Image:Chain.jpg-2.png|400px|]] | ||
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Indole-3-glycerol-phosphate (IGP) is cleaved by the tryptophan synthase α-subunit (TSA) to indole and glyceraldehyde-3-phosphate (GDP) This is known as the α-reaction. The alpha reaction is reversible. Then indole is transported via a 30 Å intermolecular tunnel to the tryptophan synthase β-subunits (TSB) that catalyze the condensation of indole and serine to tryptophan. This is known as the β-reaction and it is a pyridoxal-5-phosphate (PLP) dependent reaction. | Indole-3-glycerol-phosphate (IGP) is cleaved by the tryptophan synthase α-subunit (TSA) to indole and glyceraldehyde-3-phosphate (GDP) This is known as the α-reaction. The alpha reaction is reversible. Then indole is transported via a 30 Å intermolecular tunnel to the tryptophan synthase β-subunits (TSB) that catalyze the condensation of indole and serine to tryptophan. This is known as the β-reaction and it is a pyridoxal-5-phosphate (PLP) dependent reaction. <ref name="cite7">http://tryptophan.net/Trpsynthase/Tryptophan%20Synthase.html</ref> | ||
The substrates and ligands that bind to the various sites of tryptophan synthase cause conformational changes not only in that particular subunit, but also in the other subunits, making the complete mechanism cooperative. | |||
[[Image:TrpSyn.gif]] | [[Image:TrpSyn.gif]] | ||
===Active Sites=== | |||
[[Image:Active Site 2.gif]] | |||
α subunit reaction: The αGlu49 and αAsp60 are thought to be directly involved in the catalysis as shown.<ref name="cite7">http://tryptophan.net/Trpsynthase/Tryptophan%20Synthase.html</ref> | |||
β subunit reaction: The βLys87, βGlu109, and βSer377 are thought to be directly involved in the catalysis as shown.<ref name="cite7">http://tryptophan.net/Trpsynthase/Tryptophan%20Synthase.html</ref> | |||
==Medical Relevance== | |||
As humans do not have tryptophan synthase, this enzyme has been explored as a potential drug target. | |||
Inhibition of tryptophan synthase in amino acid metabolism has been suggested for:<ref name="info">http://en.wikipedia.org/wiki/Tryptophan_synthase</ref> | |||
• Treatment of tuberculosis | |||
• Treatment of ocular and genital infections | |||
• Treatment of cryptosporidiosis | |||
• Herbicide use | |||
==References== | ==References== | ||
<references /> | <references /> | ||
