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Sandbox Reserved 1496

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This protein consists of 2 sequence-identical polypeptide chains of 287 amino acids.
This protein consists of 2 sequence-identical polypeptide chains of 287 amino acids.
''It has 6 Magnesium ions, 2 Pyrophosphate 2-, 1 L(+)-tartaric acid and 2 (3r)-3-biphenyl-4-yl-1-azabicyclo[2.2.2]octan-3-ol as ligands''
''It has 6 Magnesium ions, 2 Pyrophosphate 2-, 1 L(+)-tartaric acid and 2 (3r)-3-biphenyl-4-yl-1-azabicyclo[2.2.2]octan-3-ol as ligands''
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Structures of BPH-651, a 3-OH quinuclidine inhibitor, bound to CrtM
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[[Image:Quinucli.jpg]]
== Biological process ==
== Biological process ==

Revision as of 19:16, 8 January 2019

This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543.
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Dehydrosqualene synthase complexed with diphosphate and quinuclidine BPH-651

Drag the structure with the mouse to rotate

Contents

Presentation of dehydrosqualene Synthase

The C30 carotene synthase CrtM enzyme is a bacterial carotenoid synthases and is involved in the first step of the subpathway that synthesizes staphyloxanthin from farnesyl diphosphate.

This subpathway is part of the pathway staphyloxanthin biosynthesis, which is itself part of carotenoid biosynthesis. Carotenoid pathways are branches of the general isoprenoid pathway.

Staphyloxanthin is a carotenoid, which is responsible for the golden color of S. aureus, and also play the role of virulence factor : it has an antioxidant action that helps the microbe evade death by reactive oxygen species produced by the host immune system. Having a better comprehension of the synthesis of this carotenoid will help to find a cure to S. aureus related diseases.


Function

Catalyzes the head-to-head condensation of two molecules of farnesyl diphosphate (FPP) into the colorless C(30) carotenoid 4,4'-diapophytoene (dehydrosqualene).

Image:CrtMcatalysa.png

Transferase Activity : Transferring alkyl or aryl groups, other than methyl groups

Metal Ion Binding : requires Mn2+ as cofactor (2 ions per subunit).

Structure

This protein consists of 2 sequence-identical polypeptide chains of 287 amino acids. It has 6 Magnesium ions, 2 Pyrophosphate 2-, 1 L(+)-tartaric acid and 2 (3r)-3-biphenyl-4-yl-1-azabicyclo[2.2.2]octan-3-ol as ligands

Structures of BPH-651, a 3-OH quinuclidine inhibitor, bound to CrtM

Image:Quinucli.jpg

Biological process

CrtM catalyses the first step of the synthesis of staphyloxanthin (with a 2-step mechanism). The catalysed reaction is : 2 (2E,6E)-farnesyl diphosphate <=> 15-cis-4,4'-diapophytoene + 2 diphosphate



Disease

This enzyme has a role to play in pathogenesis, according to the fact that staphyloxanthin is a virulence factor.

Relevance

Inhibiting the formation of staphyloxanthin is of interest in the context of developing new routes to antiinfective therapies. Cationic inhibitors are here of interest as antiinfectives because they can substitute themselves to Mg2+ and inactivate the enzyme.

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