1.6 Å Crystal Structure of the Secreted Chorismate Mutase from Mycobacterium tuberculosis: Novel Fold Topology Revealed

Ökvist, Mats; Dey, Raja; Sasso, Severin; Grahn, E.; Kast, Peter; Krengel, Ute

doi:10.1016/j.jmb.2006.01.069

Cited by 58 publications

(122 citation statements)

References 58 publications

(98 reference statements)

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“…They highlight the importance of a cationic residueeither an arginine or a lysine-proximal to the ether oxygen of the substrate in the transition state. All known natural CMs, including the structurally unrelated AroQ enzymes from Escherichia coli (19), yeast (20), and Mycobacterium tuberculosis (41,42) share this feature, whereas poor catalysts like Arg90Cit or the catalytic antibody 1F7 (43) lack it. Rather than an exception to the classic view of enzymatic catalysis, CM appears to be an archetypical example of the Pauling paradigm.…”

Section: Discussionmentioning

confidence: 99%

Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis

Burschowsky

Eerde

Ökvist

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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For more than half a century, transition state theory has provided a useful framework for understanding the origins of enzyme catalysis. As proposed by Pauling, enzymes accelerate chemical reactions by binding transition states tighter than substrates, thereby lowering the activation energy compared with that of the corresponding uncatalyzed process. This paradigm has been challenged for chorismate mutase (CM), a well-characterized metabolic enzyme that catalyzes the rearrangement of chorismate to prephenate. Calculations have predicted the decisive factor in CM catalysis to be ground state destabilization rather than transition state stabilization. Using X-ray crystallography, we show, in contrast, that a sluggish variant of Bacillus subtilis CM, in which a cationic active-site arginine was replaced by a neutral citrulline, is a poor catalyst even though it effectively preorganizes chorismate for the reaction. A series of high-resolution molecular snapshots of the reaction coordinate, including the apo enzyme, and complexes with substrate, transition state analog and product, demonstrate that an active site, which is only complementary in shape to a reactive substrate conformer, is insufficient for effective catalysis. Instead, as with other enzymes, electrostatic stabilization of the CM transition state appears to be crucial for achieving high reaction rates.pericyclic reaction | catalysis | enzyme mechanism | near attack conformation | X-ray crystal structures

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Section: Discussionmentioning

confidence: 99%

Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis

Burschowsky

Eerde

Ökvist

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…In another case, the same two genes are fused, but here, aroH I is fused to the C terminus of tyrA (tyrA-aroH I ). (Note that aroH I is well known in the literature as aroQ; consult a study by Okvist et al [56] for an alternative classification of chorismate mutase subtypes). tyrA is fused to aroF in some of the upper Gammaproteobacteria and Betaproteobacteria (see below).…”

Section: Gene Fusionsmentioning

confidence: 99%

Cohesion Group Approach for Evolutionary Analysis of TyrA, a Protein Family with Wide-Ranging Substrate Specificities

Bonner

Disz

Hwang

et al. 2008

Microbiol Mol Biol Rev

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SUMMARY Many enzymes and other proteins are difficult subjects for bioinformatic analysis because they exhibit variant catalytic, structural, regulatory, and fusion mode features within a protein family whose sequences are not highly conserved. However, such features reflect dynamic and interesting scenarios of evolutionary importance. The value of experimental data obtained from individual organisms is instantly magnified to the extent that given features of the experimental organism can be projected upon related organisms. But how can one decide how far along the similarity scale it is reasonable to go before such inferences become doubtful? How can a credible picture of evolutionary events be deduced within the vertical trace of inheritance in combination with intervening events of lateral gene transfer (LGT)? We present a comprehensive analysis of a dehydrogenase protein family (TyrA) as a prototype example of how these goals can be accomplished through the use of cohesion group analysis. With this approach, the full collection of homologs is sorted into groups by a method that eliminates bias caused by an uneven representation of sequences from organisms whose phylogenetic spacing is not optimal. Each sufficiently populated cohesion group is phylogenetically coherent and defined by an overall congruence with a distinct section of the 16S rRNA gene tree. Exceptions that occasionally are found implicate a clearly defined LGT scenario whereby the recipient lineage is apparent and the donor lineage of the gene transferred is localized to those organisms that define the cohesion group. Systematic procedures to manage and organize otherwise overwhelming amounts of data are demonstrated.

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“…1a), but PchB shows no sequence similarity to other pyruvate lyases, which proceed through a general base mechanism (16 -18). Instead, PchB shares 20% sequence identity with chorismate mutases of the AroQ family ␣ subclass, which use a Claisen rearrangement mechanism (13,19). Moreover, PchB has an additional catalytic activity as a chorismate mutase (CM) to produce prephenate (Fig.…”

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confidence: 99%

Two Crystal Structures of the Isochorismate Pyruvate Lyase from Pseudomonas aeruginosa

Zaitseva

Olechoski

et al. 2006

Journal of Biological Chemistry

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Enzymatic systems that exploit pericyclic reaction mechanisms are rare. A recent addition to this class is the enzyme PchB, an 11.4-kDa isochorismate pyruvate lyase from Pseudomonas aeruginosa. The apo and pyruvate-bound structures of PchB reveal that the enzyme is a structural homologue of chorismate mutases in the AroQ␣ class despite low sequence identity (20%). The enzyme is an intertwined dimer of three helices with connecting loops, and amino acids from each monomer participate in each of two active sites. The apo structure (2.35 Å resolution) has one dimer per asymmetric unit with nitrate bound in an open active site. The loop between the first and second helices is disordered, providing a gateway for substrate entry and product exit. The pyruvate-bound structure (1.95 Å resolution) has two dimers per asymmetric unit. One has two open active sites like the apo structure, and the other has two closed active sites with the loop between the first and second helices ordered for catalysis. Determining the structure of PchB is part of a larger effort to elucidate protein structures involved in siderophore biosynthesis, as these enzymes are crucial for bacterial iron uptake and virulence and have been identified as antimicrobial drug targets.

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1.6 Å Crystal Structure of the Secreted Chorismate Mutase from Mycobacterium tuberculosis: Novel Fold Topology Revealed

Cited by 58 publications

References 58 publications

Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis

Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis

Cohesion Group Approach for Evolutionary Analysis of TyrA, a Protein Family with Wide-Ranging Substrate Specificities

Two Crystal Structures of the Isochorismate Pyruvate Lyase from Pseudomonas aeruginosa

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