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Dynamic Hinge Regions co-localize with Biological Important Residues

This study explores the colocalization of catalytic residues with dynamic hinge regions in proteins, showing the importance of this phenomenon. The results suggest that proteins can utilize the dynamic hinge region as a catalytic center. Future work includes expanding the dataset and investigating the reasons behind the active site placement.

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Dynamic Hinge Regions co-localize with Biological Important Residues

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  1. Dynamic Hinge Regions co-localize with Biological Important Residues lecturer : Lee-Wei Yang May 21 2002

  2. Assumption : biological catalytic residues colocalized in the dynamic hinge regions of proteins. remove homologues seq.; no bias to specific protein family Method : Search Protein & inhibitor complex (randomly) PDB Literature Search Dynamic Analysis by GNM Dynamic patterns in active or inhibitory sites (Slow1,2) Residues in Active(or catalytic) site

  3. Results Table 125 proteins, their relative inhibitors and biologically critical residues Only 25 proteins out of 140 were suitable for the following study by reasons of: 1.No or insufficient inhibition or catalyst sites information in the related literature 2. Inhibitor itself is huge polypeptide with carbon number larger than 40 3.Sequences have incomplete chain information Active and inhibitor binding residues located on the hinge region of representative modes of protein motion.Except proteins in 1A42,1A5I, 1AL8, 1BH6, 1BVV, 1CRU are analyzed by global second slowest mode (slow mode 2), the rest of them were analyzed in global slowest mode (slow mode 1). Fig1 Fig2 Structure diagram of proteins and inhibitors generated by Sting Millennium Table2 Percentage score and their average for each residues in active and inhibitory sites Ex. 1ARZ

  4. Ex: Slow2 1CRU Slow1 1BH6 (by sting millennium)

  5. PDB code PDB code Active site inhibition site Amino acid Amino acid Slow1(%) 5.99 Slow1(%) 9.86 Slow2(%) 8.41 7.34 Slow2(%) B-exp(%) 15.92 B-exp(%) 17.74 Slow1avg 4.92 10.32 Slow1avg 6.05 Slow2 avg 8.63 Slow2 avg 13.91 B-exp* avg. B-exp* avg. 15.68 average of 110 points average of 161 points average of 25 proteins average of 25 proteins Table 2. Percentage score and average for residues in active and inhibitory sites AVG AVG # Inhibitory sites # Metal ions #One interesting point is that, even we did not provide inhibitor information in the GNM calculation, the hinge regions are already ready to serve as a catalytic center before the possible substrate or inhibitor binding. Discussion

  6. Conclusion This study provides a general idea of the beneficial effect that biological macromolecules set their catalytic centers in the dynamic hinge region. Future Work • Collect more proteins • Generalize the reasons for proteins which have their active • sites in the peak regions

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