Ketosteroid Isomerase: Difference between revisions
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====Beta-Turns and Loops==== | ====Beta-Turns and Loops==== | ||
β-strand 1 is connected to β-strand 2 via a four residue linkage (Pro39 to Ser42) with Pro39 being in a cis-conformation. Two examples of type-II β-turns can also be observed in KSI-between β-stands 3 & 4 (Ala75-Asn76→see figure) and β-strands 4 & 5 (Gln89-Gly90). A loop structure (Asn105-Val107) also connects β-strands 5 and 6. | β-strand 1 is connected to β-strand 2 via a <scene name='User:Laura_M._Haynes/Sandbox_1/Cis_loop/1'>four residue linkage</scene> (Pro39 to Ser42) with Pro39 being in a cis-conformation. Two examples of [http://en.wikipedia.org/wiki/Turn_%28biochemistry%29 type-II β-turns] can also be observed in KSI-between β-stands 3 & 4 (<scene name='User:Laura_M._Haynes/Sandbox_1/Turn_1/1'>Ala75-Asn76→see figure</scene>) and β-strands 4 & 5 (<scene name='User:Laura_M._Haynes/Sandbox_1/Turn_2/1'>Gln89-Gly90</scene>). A loop structure (<scene name='User:Laura_M._Haynes/Sandbox_1/Loop2/1'>Asn105-Val107</scene>) also connects β-strands 5 and 6. | ||
===Dimer Interface=== | ===Dimer Interface=== | ||
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Upon substrate binding the the three α-helices become more tightly packed with the "front face" of the β-sheet. This in turn allows Tyr14 to approach Asp99 and the substrate. | Upon substrate binding the the three α-helices become more tightly packed with the "front face" of the β-sheet. This in turn allows Tyr14 to approach Asp99 and the substrate. | ||
[[Image:morph.mov | [[Image:morph.mov]] | ||
===Cis-Peptide Bond=== | ===Cis-Peptide Bond=== | ||
Pro39 of KSI participates in a cis-peptide linkage with Asp38 in forming a <scene name='User:Laura_M._Haynes/Sandbox_1/Cis_loop/1'>four-residue linkage</scene>between stands 1 and 2 of the 6 stranded beta-sheet.<ref name="Wu" /> The cis-peptide linkage serves to correctly position the key catalytic residue Asp38 within the active site. Mutating residue to Gly or Ala results in the improper positioning of Asp38 within the active site leading to corresponding 2-fold decreases in enzyme's catalytic efficiency.<ref name="NAM">PMID:12852789 </ref> The cis-peptide bond also helps to stablize and increase the rigidity of the four-residue linkage between β-strands 1 and 2.<ref name="NAM" /> | Pro39 of KSI participates in a cis-peptide linkage with Asp38 in forming a <scene name='User:Laura_M._Haynes/Sandbox_1/Cis_loop/1'>four-residue linkage</scene>between stands 1 and 2 of the 6 stranded beta-sheet.<ref name="Wu" /> The cis-peptide linkage serves to correctly position the key catalytic residue Asp38 within the active site. Mutating residue to Gly or Ala results in the improper positioning of Asp38 within the active site leading to corresponding 2-fold decreases in enzyme's catalytic efficiency.<ref name="NAM">PMID:12852789 </ref> The cis-peptide bond also helps to stablize and increase the rigidity of the four-residue linkage between β-strands 1 and 2.<ref name="NAM" /> | ||
==Enzyme Mechanism== | ==Enzyme Mechanism== | ||
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===Structural Homologs=== | ===Structural Homologs=== | ||
As noted above, [http://en.wikipedia.org/wiki/Scytalone_dehydratase scytalone dehydratase], [http://en.wikipedia.org/wiki/NUTF2 nuclear transport factor 2 (NTF2)], and [http://en.wikipedia.org/wiki/Naphthalene_1,2-dioxygenase naphthalene 1,2-dioxygenase] share similar structural motifs to ketosteroid isomerase, which facilitate binding of hydrophobic substrates.<ref name="Ha" />,<ref name="Murzin" /> It has also been postulated that bile acid 7α-dehydratase is also a member of this family of protein and that it shares functional similarity with KSI.<ref name="Murzin" /> In a recent paper, Cherney ''et al''<ref name="Cherney">PMID:18589008 </ref>. identified ''Myobacterium tuberculosis'' Rv0760c as a structural homolog of KSI. Although these proteins share similar structural motifs there carry out a diverse array of functions.<ref name="Cherney" /> | As noted above, [http://en.wikipedia.org/wiki/Scytalone_dehydratase scytalone dehydratase], [http://en.wikipedia.org/wiki/NUTF2 nuclear transport factor 2 (NTF2)], and [http://en.wikipedia.org/wiki/Naphthalene_1,2-dioxygenase naphthalene 1,2-dioxygenase] share similar structural motifs to ketosteroid isomerase, which facilitate binding of hydrophobic substrates.<ref name="Ha" />,<ref name="Murzin" /> It has also been postulated that bile acid 7α-dehydratase is also a member of this family of protein and that it shares functional similarity with KSI.<ref name="Murzin" /> In a recent paper, Cherney ''et al''<ref name="Cherney">PMID:18589008 </ref>. identified ''Myobacterium tuberculosis'' Rv0760c as a structural homolog of KSI. Although these proteins share similar structural motifs there carry out a diverse array of functions.<ref name="Cherney" /> | ||
==Structural Classifications== | |||
===CATH=== | |||
KSI is classified using the CATH classification system as follows: | |||
# Class - Alpha Beta | |||
# Architecture - Roll | |||
# Topology - Nuclear Transport Factor 2 | |||
===SCOP=== | |||
KSI is classified using the SCOP classification system as follows: | |||
# Class - Alpha and Beta (α+β) | |||
# Fold - Cystatin-like | |||
# Superfamily - NTF2-like | |||
# Family - Ketosteroid Isomserase-like | |||
# Domian - Δ5-3-ketosteroid isomerase | |||
==Available Structures== | ==Available Structures== | ||
