Crystallization and preliminary X-ray crystallographic analysis of squalene-hopene cyclase from <i>Alicyclobacillus acidocaldarius</i>

Ku, Wendt; Feil, Corinna; Lenhart, Alexander; Poralla, Karl; Ge, Schulz

doi:10.1002/pro.5560060322

Cited by 36 publications

(30 citation statements)

References 10 publications

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“…Solubilized and partially purified pig liver and yeast oxidosqualene cyclase were obtained and the enzymatic activity determined as previously described (13,14). Recombinant squalene hopene cyclase was obtained as previously described (22).…”

Section: Methodsmentioning

confidence: 99%

Rationally designed inhibitors as tools for comparing the mechanism of squalene‐hopene cyclase with oxidosqualene cyclase

Viola

Ceruti

Cattel

et al. 2000

Lipids

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The inhibition of squalene-hopene cyclase (SHC) (E.C. 5.4.99.-), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol-like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OSC) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3-oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza-analogs of squalene and 2,3-oxidosqualene; (ii) affinity-labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.

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Section: Methodsmentioning

confidence: 99%

Rationally designed inhibitors as tools for comparing the mechanism of squalene‐hopene cyclase with oxidosqualene cyclase

Viola

Ceruti

Cattel

et al. 2000

Lipids

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“…Blasting the A. acidocaldarius SHC sequence resulted in several hundreds of potential SHC sequences, from which the top 100 sequences revealed amino acid identities of 39% to 64% and servation of structural elements, as depicted in the crystal structures of A. acidocaldarius SHC and of human OSC (94,99,101). Both structures consist of two ␣-barrel domains and show a large catalytic cavity with a channel entrance orientated to a membrane-inserted part of the enzyme (for details, see the next section).…”

Section: Occurrence Of Shcsmentioning

confidence: 99%

Squalene-Hopene Cyclases

Siedenburg

Jendrossek

2011

Appl Environ Microbiol

124

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Hopanoids and sterols are members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms. They are biochemically synthesized from linear precursors (squalene, 2,3-oxidosqualene) in only one enzymatic step that is catalyzed by squalene-hopene cyclase (SHC) or oxidosqualene cyclase (OSC). SHCs and OSCs are related in amino acid sequences and probably are derived from a common ancestor. The SHC reaction requires the formation of five ring structures, 13 covalent bonds, and nine stereo centers and therefore is one of the most complex one-step enzymatic reactions. We summarize the knowledge of the properties of triterpene cyclases and details of the reaction mechanism of Alicyclobacillus acidocaldarius SHC. Properties of other SHCs are included.

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“…All of these molecular classes are synthesized from the acyclic isoprenoid precursor, squalene (Woodward and Bloch, 1953), by a set of homologous enzymes known as polycyclic terpenoid cyclases. Such enzymes include squalene-hopene cyclase (SHC; Wendt et al, 1997) and steroidal oxidosqualene cyclase (OSC; Thoma et al, 2004). Although sterols are universal biosynthetic or dietary requirements among eukaryotes, the hopanoids of prokaryotes are irregularly distributed phylogenetically (Rohmer et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

“…SHCs can be identified readily based on their numerous conserved amino acids (AAs; Hoshino and Sato, 2002;Summons et al, 2006;Fischer and Pearson, 2007). Specific functional motifs (Feil et al, 1996;Wendt et al, 2000) and analysis of secondary structures (Wendt et al, 1997;SchulzGasch and Stahl, 2003) show that the two classes can be distinguished by sequence differences alone. There are no abiotic processes or other enzymes known to perform the functions of SHCs (Ourisson et al, 1987;Wendt et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Distribution of microbial terpenoid lipid cyclases in the global ocean metagenome

Pearson

Rusch

2008

The ISME Journal

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The bacterial terpenoid lipids known as hopanoids are fundamental tools for interpreting ancient microbial communities. Their degradation products, the hopanes, are found in sedimentary rocks throughout the geologic record. These compounds are presumed to be analogous to the sterols of eukaryotes, yet although the eukaryotic requirement for sterols is universal, hopanoid biosynthetic capacity is not ubiquitous among marine bacteria. Among the 9.8 million shotgun reads from the Sorcerer II Global Ocean Sampling (GOS) expedition, 148 contain putative coding sequence for bacterial squalene-hopene cyclases (SHCs). SHCs encoded by a-Proteobacteria potentially related to Rhodospirillaceae dominate these hits, especially in the open ocean and in tropical regions. Planctomycetes and b-Proteobacteria contribute more SHC-encoding sequences, and therefore presumably more hopanoid production, to coastal and temperate environments. Although sequences nominally related to a-and b-Proteobacteria outnumber other taxa in marine and coastal environments, there is large phylogenetic distance between GOS sequences and known species. Assuming that the environments sampled here are broadly representative of a wide range of surface ocean climates, depositional settings and temporal periods, the data suggest a fundamental function for Proteobacteria in the development of the geologic record of hopanes.

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Crystallization and preliminary X-ray crystallographic analysis of squalene-hopene cyclase from Alicyclobacillus acidocaldarius

Cited by 36 publications

References 10 publications

Rationally designed inhibitors as tools for comparing the mechanism of squalene‐hopene cyclase with oxidosqualene cyclase

Rationally designed inhibitors as tools for comparing the mechanism of squalene‐hopene cyclase with oxidosqualene cyclase

Squalene-Hopene Cyclases

Distribution of microbial terpenoid lipid cyclases in the global ocean metagenome

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