Download hinge regions are already ready to serve as a catalytic center

Dynamic Hinge Regions co-localize with
Biological Important Residues
lecturer : Lee-Wei Yang
May 21 2002
Assumption :
biological catalytic residues colocalized in
the dynamic hinge regions of proteins.
remove homologues seq.; no bias to specific protein family
Method :
PDB
Search Protein & inhibitor complex
(randomly)
Literature Search
Residues in
Active(or catalytic) site
Dynamic Analysis by GNM
Dynamic patterns in active or
inhibitory sites (Slow1,2)
Results
Table 1 25 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
Fig1 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).
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
Ex:
Slow2
1CRU
0
100 200 300 400 500 600 700 800 900 100
0
Slow1
1BH6
0
100
200
300
(by sting millennium)
Table 2. Percentage score and average for residues in active and inhibitory sites
PDB code
Active site
Amino acid
Slow1(%)
Slow2(%)
B-exp(%)
Slow1avg
Slow2 avg
B-exp* avg.
4.92
6.05
average of
25 proteins
13.91
Slow1avg
Slow2 avg
B-exp* avg.
AVG
5.99
PDB code
inhibition site
Amino acid
8.41
average of
110 points
Slow1(%)
Slow2(%)
15.92
B-exp(%)
AVG
9.86
7.34
average of
161 points
# Inhibitory sites
17.74
10.32
8.63
15.68
average of
25 proteins
Discussion
# 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.
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
1. Collect more proteins
2. Generalize the reasons for proteins which have their active
sites in the peak regions