User:Chamaya00/Sandbox

Source: Wikipedia, the free encyclopedia.
steroid delta-isomerase
Identifiers
ExPASy
NiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

In

enzymology, a steroid Delta-isomerase (EC 5.3.3.1) is an enzyme that catalyzes the chemical reaction

a 3-oxo-Delta5-steroid a 3-oxo-Delta4-steroid

Hence, this enzyme has one

substrate, 3-oxo-Delta5-steroid, and one product, 3-oxo-Delta4-steroid
.

Introduction

This enzyme belongs to the family of isomerases, specifically those intramolecular oxidoreductases transposing C=C bonds. The systematic name of this enzyme class is 3-oxosteroid Delta5-Delta4-isomerase. Other names in common use include ketosteroid isomerase (KSI), hydroxysteroid isomerase, steroid isomerase, Delta5-ketosteroid isomerase, Delta5(or Delta4)-3-keto steroid isomerase, Delta5-steroid isomerase, 3-oxosteroid isomerase, Delta5-3-keto steroid isomerase, and Delta5-3-oxosteroid isomerase.

KSI has been studied extensively from the bacteria Comamonas testosteroni (TI), formerly referred to as Pseudomonas testosteroni, and Pseudomonas putida (PI) [1]. Mammalian KSI has been studied from bovine adrenal cortex [2] and rat liver [3]. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism. An example substrate is delta-5-androstene-3,17-dione, which KSI converts to delta-4-androstene-3,17-dione [4]. The above reaction in the absence of enzyme takes 7 weeks to complete in aqueous solution [5]. KSI performs this reaction on an order of 1011 times faster, ranking it among the most proficient enzymes known [5]. Bacterial KSI also serves as a model protein for studying enzyme catalysis[6] and protein folding[7].

Structural Studies

KSI exists as a

hydrophobic substrates, suggesting this fold is characteristic for binding hydrophobic substrates [9]
.

As of late 2007, 25

structures have been solved for this class of enzymes, with PDB accession codes 1BUQ, 1C7H, 1CQS, 1DMM, 1DMN, 1DMQ, 1E97, 1GS3, 1ISK, 1K41, 1OCV, 1OGX, 1OGZ, 1OH0, 1OHO, 1OHP, 1OHS, 1OPY, 1VZZ, 1W00, 1W01, 1W02, 1W6Y, 2PZV, and 8CHO
.

Mechanism

The conversion of a Delta-5 steroid to a conjugated system Delta-4 steroid begins with Asp-38 abstracting a hydrogen at the 4 position to form an enolate [1]. Asp-38 then transfers the proton proton to the 6 position to give the product [1]. There have been conflicting results on the

thermodynamic argument to suggest the intermediate exists as the enolate [1]
. Also of contention is the nature of the hydrogen bonding network stabilizing the reaction intermediate, whether Tyr-14 and Asp-99 both form hydrogen bonds directly to the O-3 [12] or Asp-99 hydrogen bonds to Tyr-14 which hydrogen bonds to O-3 [13].

Biological Function

KSI occurs in animal tissues concerned with

testis, and ovary [14]. KSI in Comamomas testosteroni is used in the degradation pathway of steroids, allowing this bacteria to utilize steroids containing a double bond at delta-5, such as testosterone, as its sole source of carbon [15]
.

Model Enzyme

KSI has been used as a model system to test different theories to explain how enzymes achieve their catalytic efficiency.

pKa values for the catalytic residues have been proposed as the basis for the fast action of KSI [9]. Another proposal explaining enzyme catalysis tested through KSI is the geometrical complementarity of the active site to the transition state, which proposes the active site electrostatics is complementary to the substrate transition state [6]
. KSI has also been a model system for studying protein folding. Kim et al. studied the effect of folding and
tertiary structure on the function of KSI [7]
.

References

  1. ^ a b c d Pollack, R. M. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg. Chem. 2004, 32, 341-353.
  2. ^ Bertolino, A.; Benson, A. M.; Talalay, P. Activation of Delta-5-3-Ketosteroid Isomerase of Bovine Adrenal Microsomes by Serum Albumins. Biochem. Biophys. Res. Commun. 1979, 88, 1158-1166.
  3. ^ Benson, A. M.; Talalay, P. Role of Reduced Glutathione in Delta-5-3-Ketosteroid Isomerase Reaction of Liver. Biochem. Biophys. Res. Commun. 1976, 69, 1073-1079. PubMed Full Text
  4. ^ Talalay, P.; Benson, A. M. In 18 Δ5-3-Ketosteroid Isomerase; Paul D. Boyer, Ed.; The Enzymes; Academic Press: 1972; Vol. Volume 6, pp 591-618.
  5. ^ a b Radzicka, A.; Wolfenden, R. A Proficient Enzyme. Science 1995, 267, 90-93. PubMed
  6. ^ a b Kraut, D. A.; Sigala, P. A.; Pybus, B.; Liu, C. W.; Ringe, D.; Petsko, G. A.; Herschlag, D. Testing electrostatic complementarity in enzyme catalysis: Hydrogen bonding in the ketosteroid isomerase oxyanion hole. PLoS. Biol. 2006, 4, 501-519. PMC Full Text
  7. ^ a b c d Kim, D. H.; Nam, G. H.; Jang, D. S.; Yun, S.; Choi, G.; Lee, H. C.; Choi, K. Y. Roles of dimerization in folding and stability of ketosteroid isomerase from Pseudomonas putida biotype B. Protein Sci. 2001, 10, 741-752. PMC Full Text
  8. ^ Kim, S. W.; Cha, S. S.; Cho, H. S.; Kim, J. S.; Ha, H. C.; Cho, M. J.; Joo, S.; Kim, K. K.; Choi, K. Y.; Oh, B. H. High-resolution crystal structures of Delta(5)-3-ketosteroid isomerase with and without a reaction intermediate analogue. Biochemistry (N. Y. ) 1997, 36, 14030-14036 PubMed. cited in Kim, D. H.; Nam, G. H.; Jang, D. S.; Yun, S.; Choi, G.; Lee, H. C.; Choi, K. Y. Roles of dimerization in folding and stability of ketosteroid isomerase from Pseudomonas putida biotype B. Protein Sci. 2001, 10, 741-752.
  9. ^ a b Ha, N. C.; Choi, G.; Choi, K. Y.; Oh, B. H. Structure and enzymology of Delta(5)-3-ketosteroid isomerase. Curr. Opin. Struct. Biol. 2001, 11, 674-678. PubMed Full Text
  10. ^ Xue, L.; Kuliopulos, A.; Mildvan, A. S.; Talalay, P. Catalytic Mechanism of an Active-Site Mutant (D38n) of Delta-5-3-Ketosteroid Isomerase - Direct Spectroscopic Evidence for Dienol Intermediates. Biochemistry (N. Y. ) 1991, 30, 4991-4997 PubMed. cited in Pollack, R. M. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg. Chem. 2004, 32, 341-353.
  11. ^ Petrounia, I. P.; Pollack, R. M. Substituent effects on the binding of phenols to the D38N mutant of 3-oxo-Delta(5)-steroid isomerase. A probe for the nature of hydrogen bonding to the intermediate. Biochemistry (N. Y. ) 1998, 37, 700-705. PubMed. cited in Pollack, R. M. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg. Chem. 2004, 32, 341-353.
  12. ^ Wu, Z. R.; Ebrahimian, S.; Zawrotny, M. E.; Thornburg, L. D.; PerezAlvarado, G. C.; Brothers, P.; Pollack, R. M.; Summers, M. F. Solution structure of 3-oxo-Delta(5)-steroid isomerase. Science 1997, 276, 415-418. cited in Pollack, R. M. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg. Chem. 2004, 32, 341-353. PubMed
  13. ^ Zhao, Q. J.; Abeygunawardana, C.; Gittis, A. G.; Mildvan, A. S. Hydrogen bonding at the active site of Delta(5)-3-ketosteroid isomerase. Biochemistry (N. Y. ) 1997, 36, 14616-14626. PubMed. cited in Pollack, R. M. Enzymatic mechanisms for catalysis of enolization: ketosteroid isomerase. Bioorg. Chem. 2004, 32, 341-353.
  14. ^ Kawahara, F. S. Delta-5-3-Ketosteroid Isomerase from Pseudomonas-Testosteroni. Meth. Enzymol. 1962, 5, 527-532.
  15. ^ Talalay, P.; Dobson, M. M.; Tapley, D. F. Oxidative Degradation of Testosterone by Adaptive Enzymes. Nature 1952, 170, 620-621. PubMed
  • Ewald W, Werbin H, Chaikoff IL (1965). "Evidence for the presence of 17-hydroxypregnenedione isomerase in beef adrenal cortex". Biochim. Biophys. Acta. 111 (1): 306–12.
    PMID 5867327.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  • Kawahara FS and Talalay P (1960). "Crystalline Delta5-3-ketosteroid isomerase". J. Biol. Chem. 235: PC1–PC2.
  • Talalay P and Wang VS (1955). "Enzymic isomerization of Delta5-3-ketosteroids". Biochim. Biophys. Acta. 18: 300–301.
    PMID 13276386
    .
  • Steroid+Isomerases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This isomerase article is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Chamaya00/Sandbox&oldid=527646913"