From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models PDB ID 2f6l Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2f6l, resolution 1.70Å ()
Gene:	Rv1885c (Mycobacterium tuberculosis)
Activity:	Chorismate mutase, with EC number 5.4.99.5
Structural annotation: Resources: InterPro : Ipr002701, Ipr008240 Pfam : PF01817 SCOP : d2f6la1, d2f6lb1 UniProt : O07746
Functional annotation: Biological process: aromatic amino acid family biosynthetic process Molecular function: chorismate mutase activity
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada.

To get started: Click the edit this page tab at the top. Save the page after each step, then edit it again. Click the 3D button (when editing, above the wikitext box) to insert Jmol. show the Scene authoring tools, create a molecular scene, and save it. Copy the green link into the page. Add a description of your scene. Use the buttons above the wikitext box for bold, italics, links, headlines, etc. More help: Help:Editing

Contents 1 Chorismate Mutase 1.1 Introduction 1.2 Structure 1.3 Mechanism 1.4 Chorismate Mutase and Tuberculosis 1.5 References

Chorismate Mutase

Introduction

The gene Rv1885c from Mycobacteriam tuberculosis encodes for a non-functional chorismate mutase (*MtCM)^[1]. This non-functional mutase has a 33-amino-acid cleavable sequence. It is a vital enzyme in the shikimate pathway, which allows for the synthesis of tryptophan, tyrosinem and phenylalanine ^[1]. Chorismate mutase only occurs in bacteria, higher plants, and fungi, due to the fact that the shikimate pathway is only found in these organisms ^[2]. In Escherichia coli, chorismate mutase has a periplasmic destination^[1]. In M. tuberculosis there is in abscence of a periplasmic compartment for chorismate mutase, so it secretes into the culture filtrate of M. tuberculosis^[1]. It is believed that a pseudoperiplasmic space might exist in M. tuberculosis^[1] Rv1185c is synthesized along with an amino acid terminal sequence, which is cleaved off from the mature protein when expressed with e coli

Chorismate mutase is an essential enzyme in the shikimate pathway ^[1]. This pathway allows for the biosynthesis of aromatic amino acids tryptophan, tyrosine, and phenylalanine ^[1]. The production of tyrosine and phenylalanine is achieved by what is called a Claisen arrangement. first converting chorismate to prephenate. Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate. After this occursm aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine. Chorismate mutase provides a 2x10⁶ fold increase in the rate of reaction, in comparison to the uncatalyzed reaction ^[3]. It is the only example of an enzyme catalyzing a percyclic reaction ^[2]

Structure

spinqualitylabelsall models Insert caption here Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

has dimeric state in concentrations as low as 5nM has an all alpha helical structure active site forms in single chain without help from second half of dimer active site is critical for catalysis. it is made up of Arg 49, Lys 60, Arg 72, Thr 105, Glu 109, and Arg 134 not regulated by aromatic amino acids, which is supported by the fact that there are no allosteric regulatory sites.

alpha helicalstruc similar to e coli CM and S. cerevisae CM

here is a

Mechanism

in michaelis menten kinetics it has Km of 0.5 ± 0.05 mM and Kcat of 60 s^-1 Chorismate mutase is an essential enzyme in the shikimate pathway ^[1]. This pathway allows for the biosynthesis of aromatic amino acids tryptophan, tyrosine, and phenylalanine ^[1]. The production of tyrosine and phenylalanine is achieved by what is called a Claisen arrangement. first converting chorismate to prephenate. Prephenate then reacts with prephenate dehydratase and prephenate dehydrogenase which forms phenylpyruvate and hydroxyphenylpyruvate. After this occursm aminotransferase converts hydroxy-phenylpyruvate and phenylpyruvate to phenylalanine and tyrosine. Chorismate mutase provides a 2x10⁶ fold increase in the rate of reaction, in comparison to the uncatalyzed reaction ^[4]. It is the only example of an enzyme catalyzing a percyclic reaction ^[2]

Chorismate Mutase and Tuberculosis

may be involved in pathogenesis. one can take advantage of non-occurance of CMs in humans to try to develop antimicrobial drugs for human pathogens such as tb

References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8} Kim SK, Reddy SK, Nelson BC, Vasquez GB, Davis A, Howard AJ, Patterson S, Gilliland GL, Ladner JE, Reddy PT. Biochemical and structural characterization of the secreted chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv: an *AroQ enzyme not regulated by the aromatic amino acids. J Bacteriol. 2006 Dec;188(24):8638-48. PMID:17146044 doi:188/24/8638
2. ↑ ^{2.0 2.1 2.2} Kast P, Grisostomi C, Chen IA, Li S, Krengel U, Xue Y, Hilvert D. A strategically positioned cation is crucial for efficient catalysis by chorismate mutase. J Biol Chem. 2000 Nov 24;275(47):36832-8. PMID:10960481 doi:10.1074/jbc.M006351200
3. ↑ P.D. Lyne, A.J. Mulholland, W.G. Richards. Insights into chorismate mutase catalysis from a combined qm/mm simulation of the enzyme reaction. Journal of the American Chemistry Society. 1995 117(45):11345-11350
4. ↑ P.D. Lyne, A.J. Mulholland, W.G. Richards. Insights into chorismate mutase catalysis from a combined qm/mm simulation of the enzyme reaction. Journal of the American Chemistry Society. 1995 117(45):11345-11350