Molecular dynamic study of orotidine-5′-monophosphate decarboxylase in ground state and in intermediate state: A role of the 203–218 loop dynamics

Hur, Sun; Bruice, Thomas C.

doi:10.1073/pnas.142307099

Cited by 33 publications

(30 citation statements)

References 18 publications

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“…The loop ( Figure 4A ) is in open conformation when it is ordered and in closed conformation at the active site contacting the ligand [31] . Hur and Bruice performed MD simulations and found that the loop changes conformation during the catalytic reaction [32] .…”

Section: Resultsmentioning

confidence: 99%

Coupling between Catalytic Loop Motions and Enzyme Global Dynamics

et al. 2012

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Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops. Our dataset includes a total of 117 crystal structures for ten enzymes of different sizes and oligomerization states. Each enzyme contains a specific functional/catalytic loop (10–21 residues long) that closes over the active site during catalysis. Principal component analysis (PCA) of the available crystal structures (including apo and ligand-bound forms) for each enzyme revealed the dominant conformational changes taking place in these loops upon substrate binding. These experimentally observed loop reconfigurations are shown to be predominantly driven by energetically favored modes of motion intrinsically accessible to the enzyme in the absence of its substrate. The analysis suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site.

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Section: Resultsmentioning

confidence: 99%

Coupling between Catalytic Loop Motions and Enzyme Global Dynamics

et al. 2012

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“…Currently, the most accredited mechanisms involve direct decarboxylation of OMP (21). This was proposed based on X-ray analysis of the structure of OMPDCinhibitor complexes (22)(23)(24)(25)(26)(27)(28), and is supported by a wealth of theoretical and experimental studies (22,(29)(30)(31). It has been proposed that the protonation/decarboxylation of OMP could be a concerted event at the direct decarboxylation (23).…”

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confidence: 99%

Structural Basis for the Decarboxylation of Orotidine 5'-Monophosphate (OMP) by Plasmodium Falciparum OMP Decarboxylase

Tokuoka

Kusakari²,

Krungkrai³

et al. 2007

Journal of Biochemistry

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Orotidine 5'-monophoshate decarboxylase (OMPDC) catalyses the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP). Here, we report the X-ray analysis of apo, substrate or product-complex forms of OMPDC from Plasmodium falciparum (PfOMPDC) at 2.7, 2.65 and 2.65 A, respectively. The structural analysis provides the substrate recognition mechanism with dynamic structural changes, as well as the rearrangement of the hydrogen bond array at the active site. The structural basis of substrate or product binding to PfOMPDC will help to uncover the decarboxylation mechanism and facilitate structure-based optimization of antimalarial drugs.

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“…In fact, numerous TIM-barrel enzymes exhibit some sort of loop flexibility which is sometimes intimately coupled with catalysis. [16][17][18] A similarly disordered region to that noted for GcnA (in this case the polypeptide chain immediately following the two catalytic acids) is also observed in the AaDspB structure 9 Coincidentally, AaDspB also contains an acetate ion in the active site pocket in the same position as that observed in active GcnA.…”

Section: Discussionmentioning

confidence: 54%