Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase
The opening/closure of the catalytic loop 6 over the active site in apo triosephosphate isomerase (TIM) has been previously shown to be driven by the global motions of the enzyme, specifically the counter-clockwise rotation of the subunits. In this work, the effect of the substrate dihydroxyacetone...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2013-03-01
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| Series: | Entropy |
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| Online Access: | http://www.mdpi.com/1099-4300/15/3/1085 |
| _version_ | 1798003632269950976 |
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| author | Pemra Doruker Zeynep Kurkcuoglu |
| author_facet | Pemra Doruker Zeynep Kurkcuoglu |
| author_sort | Pemra Doruker |
| collection | DOAJ |
| description | The opening/closure of the catalytic loop 6 over the active site in apo triosephosphate isomerase (TIM) has been previously shown to be driven by the global motions of the enzyme, specifically the counter-clockwise rotation of the subunits. In this work, the effect of the substrate dihydroxyacetone phosphate (DHAP) on TIM dynamics is assessed using two apo and two DHAP-bound molecular dynamics (MD) trajectories (each 60 ns long). Multiple events of catalytic loop opening/closure take place during 60 ns runs for both apo TIM and its DHAP-complex. However, counter-clockwise rotation observed in apo TIM is suppressed and bending-type motions are linked to loop dynamics in the presence of DHAP. Bound DHAP molecules also reduce the overall mobility of the enzyme and change the pattern of orientational cross-correlations, mostly those within each subunit. The fluctuations of pseudodihedral angles of the loop 6 residues are enhanced towards the C-terminus, when DHAP is bound at the active site. |
| first_indexed | 2024-04-11T12:12:08Z |
| format | Article |
| id | doaj.art-bf4bf3c354e947c8ba4cbf8c4f03a028 |
| institution | Directory Open Access Journal |
| issn | 1099-4300 |
| language | English |
| last_indexed | 2024-04-11T12:12:08Z |
| publishDate | 2013-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Entropy |
| spelling | doaj.art-bf4bf3c354e947c8ba4cbf8c4f03a0282022-12-22T04:24:36ZengMDPI AGEntropy1099-43002013-03-011531085109910.3390/e15031085Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate IsomerasePemra DorukerZeynep KurkcuogluThe opening/closure of the catalytic loop 6 over the active site in apo triosephosphate isomerase (TIM) has been previously shown to be driven by the global motions of the enzyme, specifically the counter-clockwise rotation of the subunits. In this work, the effect of the substrate dihydroxyacetone phosphate (DHAP) on TIM dynamics is assessed using two apo and two DHAP-bound molecular dynamics (MD) trajectories (each 60 ns long). Multiple events of catalytic loop opening/closure take place during 60 ns runs for both apo TIM and its DHAP-complex. However, counter-clockwise rotation observed in apo TIM is suppressed and bending-type motions are linked to loop dynamics in the presence of DHAP. Bound DHAP molecules also reduce the overall mobility of the enzyme and change the pattern of orientational cross-correlations, mostly those within each subunit. The fluctuations of pseudodihedral angles of the loop 6 residues are enhanced towards the C-terminus, when DHAP is bound at the active site.http://www.mdpi.com/1099-4300/15/3/1085molecular dynamics simulationessential dynamicscollective motionsfunctional loop dynamicstriosephosphate isomerasedihydroxyacetone phosphateloop closure |
| spellingShingle | Pemra Doruker Zeynep Kurkcuoglu Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase Entropy molecular dynamics simulation essential dynamics collective motions functional loop dynamics triosephosphate isomerase dihydroxyacetone phosphate loop closure |
| title | Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase |
| title_full | Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase |
| title_fullStr | Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase |
| title_full_unstemmed | Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase |
| title_short | Substrate Effect on Catalytic Loop and Global Dynamics of Triosephosphate Isomerase |
| title_sort | substrate effect on catalytic loop and global dynamics of triosephosphate isomerase |
| topic | molecular dynamics simulation essential dynamics collective motions functional loop dynamics triosephosphate isomerase dihydroxyacetone phosphate loop closure |
| url | http://www.mdpi.com/1099-4300/15/3/1085 |
| work_keys_str_mv | AT pemradoruker substrateeffectoncatalyticloopandglobaldynamicsoftriosephosphateisomerase AT zeynepkurkcuoglu substrateeffectoncatalyticloopandglobaldynamicsoftriosephosphateisomerase |