Compute chemistry - enzyme function
title:
short title:
Computational Biology 2 - Protein function:
cb2_enzymes
Protein Prediction 2 - Protein function
Computational Biology 2 - TUM Winter 2014/15
lecture: © Burkhard Rost
1 /00
CONTACT: Tanya Goldberg [email protected]
Announcements
Videos:
YouTube / www.rostlab.org
THANKS :
Tim Karl + Jonas Reeb
Special lectures:
• 10/28 & 30 - Tobias Hamp
• 11/20 - Tatyana Goldberg (to confirm)
• 12/16&18 - Andrea Schafferhans
Tim
Karl
Jonas
Reeb
No lecture:
• Nov 04 Tue (Student assembly)
• Dec 04 Thu (TUM Dies Academicus)
LAST lecture: Examen: • Makeup:
January 20
January 22
Apr 14, 2015 - morning/noon
Tatyana
Goldberg
© Burkhard Rost
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Recap:
homology-based
inference
© Burkhard Rost
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Homology-inference
R Nair & B Rost 2002 Protein Science 11, 2836-47
B Rost 2002 J Mol Biol 318, 595-608
B Rost 1999 Prot Engng 12, 85-94
© Burkhard Rost
4 /00
Translocator protein
tspO - Rhodobacter sphaeroides MMNMDWALFLTFLAACGAPATTGALLKPDEWYDNLNKPWWNPPRWVFPLAWTSLYFLMSL
AAMRVAQLEGSGQALAFYAAQLAFNTLWTPVFFGMKRMATALAVVMVMWLFVAATMWAFF
QLDTWAGVLFVPYLIWATAATGLNFEAMRLNWNRPEARA
Tspo - Rattus norvegicus
MSQSWVPAVGLTLVPSLGGFMGAYFVRGEGLRWYASLQKPSWHPPRWTLAPIWGTLYSAM
GYGSYIIWKELGGFTEEAMVPLGLYTGQLALNWAWPPIFFGARQMGWALVDLMLVSGVAT
ATTLAWHRVSPPAARLLYPYLAWLAFATMLNYYVWRDNSGRRGGSRLTE
tsp0-RS
Tspo-rat
31
33
WYDNLNKPWWNPPRWVFPLAWTSLYFLMSLAAMRVAQ-----LEGSGQALAFYAAQLAFN
WYASLQKPSWHPPRWTLAPIWGTLYSAMGYGSYIIWKELGGFTEEAMVPLGLYTGQLALN
** * ** * ****
* ** *
*
* * *** *
tsp0-RS
Tspo-rat
86
93
TLWTPVFFGMKRMATALAVVMVMWLFVAATMWAFFQLDTWAGVLFVPYLIWATAATGLNF
WAWPPIFFGARQMGWALVDLMLVSGVATATTLAWHRVSPPAARLLYPYLAWLAFATMLNY
* * ***
* **
*
** *
* * *** *
** **
tsp0-RS 146 EAMRLNWNR
Tspo-rat 153 YVWRDNSGR
* * *
© Burkhard Rost
5 /00
?
Translocator protein
tspO - Rhodobacter sphaeroides MMNMDWALFLTFLAACGAPATTGALLKPDEWYDNLNKPWWNPPRWVFPLAWTSLYFLMSL
AAMRVAQLEGSGQALAFYAAQLAFNTLWTPVFFGMKRMATALAVVMVMWLFVAATMWAFF
QLDTWAGVLFVPYLIWATAATGLNFEAMRLNWNRPEARA
Same function
Tspo - Rattus norvegicus
MSQSWVPAVGLTLVPSLGGFMGAYFVRGEGLRWYASLQKPSWHPPRWTLAPIWGTLYSAM
GYGSYIIWKELGGFTEEAMVPLGLYTGQLALNWAWPPIFFGARQMGWALVDLMLVSGVAT
ATTLAWHRVSPPAARLLYPYLAWLAFATMLNYYVWRDNSGRRGGSRLTE
tsp0-RS
Tspo-rat
31
33
WYDNLNKPWWNPPRWVFPLAWTSLYFLMSLAAMRVAQ-----LEGSGQALAFYAAQLAFN
WYASLQKPSWHPPRWTLAPIWGTLYSAMGYGSYIIWKELGGFTEEAMVPLGLYTGQLALN
** * ** * ****
* ** *
*
* * *** *
tsp0-RS
Tspo-rat
86
93
TLWTPVFFGMKRMATALAVVMVMWLFVAATMWAFFQLDTWAGVLFVPYLIWATAATGLNF
WAWPPIFFGARQMGWALVDLMLVSGVATATTLAWHRVSPPAARLLYPYLAWLAFATMLNY
* * ***
* **
*
** *
* * *** *
** **
tsp0-RS 146 EAMRLNWNR
Tspo-rat 153 YVWRDNSGR
* * *
© Burkhard Rost
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Shapers and Shakers
Dame Janet Maureen Thornton
Dame, DBE, FRS FMedSci
Director
EBI (European Bioinformatics Institute, Hinxton, Cambridgeshire, England)
BS Physics (Univ Nottingham), MS Biophysics King’s
College London, PhD Biophysics UCL
Janet Thornton
Amongst Top 100 scientists in UK
~400 publications
1 with over 11,000 quotes
7 with over 1,000 quotes
81 with over 100 quotes
H-index >88 (ISI 2011/05)
© Burkhard Rost
Wikepedia
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Janet Thornton’s keynote in Istanbul
Biophysical Society Thematic Meeting in Istanbul
September 10-14, 2014 , Koc University, Istanbul, Turkey Modeling of Biomolecular Systems …
Organizers:
Ivet Bahar, U Pittsburgh, USA & Ozlem Keskin, Koc U, Turkey
© Burkhard Rost
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Computing
chemistry:
enzymatic activity
(slides from Janet Thornton)
© Burkhard Rost
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© Janet Thornton
EMBL-EBI
© Janet Thornton
EMBL-EBI
© Burkhard Rost
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The Evolution of Enzymes & Functional Diversity
Janet Thornton
European Bioinformatics
Institute
EMBL-EBI
© Burkhard Rost
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Recap: Mapping Enzyme Function (EC) to Proteins
1 Enzyme
Function
1 Enzyme
Function
1 Enzyme
Family
1 Enzyme
Function
Enzyme
Function 1
Enzyme
Function 2
Enzyme
Function 3
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Aspartate amino transferase superfamily
77
11
2.6.1.1
6
73
4.1.99.2
76 10
Aspartate Aminotransferase
7
76
Tyrosine Phenolyase
9
79
7
77
4.1.1.64
2,2-Dialkylglycine
Decarboxylase
4.1.1.17
Ornithine Decarboxylase
© Janet Thornton © Burkhard
Rost
EMBL-EBI
13 /00
Two modes of evolution of enzyme function
change substrate but
change chemistry but
&
conserve chemistry
conserve substrate-binding
Alanine racemase
EC 5.1.1.1
Methionine racemase
EC 5.1.1.2
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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GOAL
To discover how enzyme function in a family
changes during evolution as the sequence
changes:
We require knowledge of:
• Sequences (+ preferably structures as well)
• Experimental determination of Enzyme Functions
Plus Computational tools to describe and
compare enzyme functions
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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FunTree map of enzyme function and
evolution
Nick Furnham
et al.
& Janet Thornton
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
16 /00
Capturing Sequence & Function Evolution
The FunTree pipeline
Nick Furnham
Collaboration with Christine Orengo, UCL
A Furnham, et al., CA Orengo & JM Thornton (2012)
PLoS Comp Biol 8:e1002403
©
©Janet
Janet
Thornton
© Burkhard
Rost Thornton
EMBL-EBI
EMBL-EBI
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Building trees to explore the evolution of
enzyme function
Clustering structural domains and gathering sequence
Structurally-informed multiple sequence
Phylogenetic analysis
Functional annotation
http://www.ebi.ac.uk/thornton-srv/databases/
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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An example Superfamily:
Phosphatidylinositol phosphodiesterase (PIPDE) superfamily
Superfamily in numbers:
• 8843 proteins, with10187 domains • in 2748 Species
- 26 in homo sapiens • 39 structures (PDB)
• 18 enzyme functions & 212 GO terms
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Phosophatidylinositol phosphodiesterase (PIPDE) superfamily:
PIPDE domain architectures
•This domain combines with many (81)
different domains
• 280 Multi-Domain Architectures
• Only 25 in UniProtKB
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
20 /00
Phosophatidylinositol phosphodiesterase (PIPDE) superfamily:
e.g. one member: PLC (phosphoinositide phospholipase C)
• Eukaryotic intracellular enzymes
• Catalyzes the hydrolysis of PIP2 into two
important 2nd messenger molecules
• Involved in PIP2 metabolism and lipid
signaling pathways
•Affects proliferation, differentiation,
apoptosis and neurotransmission.
• Also found in bacteria and
trypanosomes.
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Function of PLC: EC=3.1.4.11 Phosphoinositide phospholipase C
This enzyme cleaves off one end of the molecule
using a hydrolase reaction to split an O-P bond
Mg
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Phosophatidylinositol phosphodiesterase (PIPDE) superfamily
18 Different Enzyme Functions including Transferases, Hydrolases, Lyases
2.4.1.18 N-acetylglucosaminyldiphosphoundecaprenol N-acetyl-beta-D- mannosaminyltransferase.
2.7.7.48 RNA-directed RNA polymerase.
3.1.1.5
3.1.22.1
3.1.3.1
3.1.4.11
3.1.4.13
3.1.4.3
3.1.4.4
3.1.4.41
3.1.4.43
Lysophospholipase
Deoxyribonuclease II.
Alkaline phosphatase.
Phosphoinositide phospholipase C.
Serine-ethanolaminephosphate phosphodiesterase.
Phospholipase C.
Phospholipase D.
Sphingomyelin phosphodiesterase D.
Glycerophosphoinositol inositolphosphodiesterase.
3.1.4.44
3.1.4.46
3.2.1.14
3.2.1.73
3.4.11.4
Glycerophosphoinositol glycerophosphodiesterase.
Glycerophosphodiester phosphodiesterase.
Chitinase.
Licheninase.
Tripeptide aminopeptidase.
Active Site
10 structures superposed
4.6.1.13 Phosphatidylinositol diacylglycerol-lyase.
4.6.1.14 Glycosylphosphatidylinositol diacylglycerol-lyase.
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Phosophatidylinositol phosphodiesterase superfamily:
Evolutionary sequence tree
4.6.1.13
Phosphatidylinositol diacylglycerol-lyase. PDL
4.6.1.14
Glycosylphosphatidylinositol diacylglycerol-lyase.
3.1.4.41
Sphingomyelin phosphodiesterase D. (+Ca) SPD
3.1.4.46
Glycerophosphodiester phosphodiesterase.
3.1.4.4
Phospholipase D.
3.1.4.46
Glycerophosphodiester phosphodiesterase.
3.1.4.44
Glycerophosphoinositol glycerophosphodiesterase.
3.1.4.43
Glycerophosphoinositol inositolphosphodiesterase.
3.1.4.11
Phosphoinositide phospholipase C (+Mg). PLC
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
24 /00
Phosophatidylinositol phosphodiesterase superfamily:
Three members of PIPDE with different functions
4.6.1.13
Phosphatidylinositol
diacylglycerol-lyase
PDL. – no metal
3.1.4.41
Sphingomyelin
phosphodiesterase D
SPD. (Ca)
3.1.4.11
Phosphoinositide
phospholipase C
(PLC). (Ca)
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
25 /00
Phosophatidylinositol phosphodiesterase superfamily:
Three members of PIPDE with different functions
Phosphatidylinositol diacylglycerol-lyase (PDL)
4.6.1.13
Sphingomyelin phosphodiesterase D (SPD)
3.1.4.41
Mg
Phosphoinositide phospholipase C. (PLC)
3.1.4.11
3.1.4.11
Ca
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
26 /00
Phosophatidylinositol phosphodiesterase (PIPDE) superfamily:
Different functions - similar chemistry
3.1.4.41
Mg
Sphingomyelin phosphodiesterase D - SPD.
I3P
SPD
I3P
PLC
3.1.4.11
Ca
Phosphoinositide phospholipase C - PLC.
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
27 /00
Phosophatidylinositol phosphodiesterase (PIPDE) superfamily:
Change in substrate
E.C. 3.1.4.41
Sphingomyelin phosphodiesterase D.
SPD (Mg)
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
E.C. 3.1.4.11
Phosphoinositide phospholipase C.
PLC (Ca)
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Phosophatidylinositol phosphodiesterase (PIPDE) superfamily:
Change in chemistry
4.6.1.13
PDL
PDL
PLC
3.1.4.11
Ca
PLC
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
29 /00
Phosophatidylinositol phosphodiesterase (PIPDE) superfamily:
Aspartic acid (D) -> Arginine (R): loss of metal binding
E.C. 3.1.4.11
E.C. 3.1.4.41
E.C. 4.6.1.13
…..
…..
E.C. 3.1.4.11
E.C. 3.1.4.41
E.C. 4.6.1.13
D to R
…..
E.C. 3.1.4.11
E.C. 3.1.4.41
E.C. 4.6.1.13
3.1.4.11 PLC + Ca
E.C. 3.1.4.11
E.C. 3.1.4.41
E.C. 4.6.1.13
3.1.4.41 SPD + Mg
4.6.1.13 PDL
E.C. 3.1.4.11
E.C. 3.1.4.41
E.C. 4.6.1.13
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
30 /00
Phosophatidylinositol phosphodiesterase superfamily:
Sequence+structure tree capture EC function
Analysis of 276
enzyme families
E.C. Exchange Matrix
# changes within same E.C. class = 2967 (89%)
i.e. changes in substrates
# changes between E.C. classes = 360 (11%)
i.e. changes in chemistry of reaction
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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EC-BLAST
S Asad Rahman
et al.
& Janet Thornton
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
32 /00
Capture enzyme function in silico
EC-BLAST: a tool to automatically search
and compare enzyme reactions
Asad
Rahman
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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EC numbers classify enzymes
Four digit hierarchical classification of enzyme reactions
Preformed manually by Enzyme Commission (EC)
C. SC. SSC. SN
Class
Class 1.
2.
3.
4.
5.
6.
Oxidoreductase
Transferase
Hydrolase
Lyase
Isomerase
Ligase
Serial Number
Sub-class
&
Sub-subclass
e.g. Phosphoinositide phospholipase C
EC 3.1.4.11
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
34 /00
Formalizing enzyme reactions
To do this automatically we need
• Atom-Atom Mapping – across a reaction
• A quantitative measure of reaction similarity (cf
•
Sequence Identity or RMSD)
A Tool to compare reactions (cf BLAST & SSAP)
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
35 /00
Extracting Reaction Mechanism (Dugundji-Ugi Model B+E=R 1973)
.1.
.2.
.1.
R
.7.
.2.
.3.
.6.
.3.
.5. .4.
1
2
3
4
5
6
4
2
3
6
4
1
6
7
7
4
1
1
2
3
4
5
6
BE-matrix (Product )
1
7
1
1
1
2
2
1
3
-2
4
1
1
1
2
.5.
2
1
5
.6.
.4.
R-matrix (Reaction)
BE-matrix (Educt )
1
.7.
1
Free valence
Order of a bond electrons
2
3
4
5
4
1
4
-1
4
1
2
5
6
6
6
1
7
7
5
-1
Changes in free valence electrons
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
7
2
3
1
6
2
1
1
1
1
1
Changes in order of a bond
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Store all Mapped Reactions in the Database
Reaction centres
Bond changes incl.
stereochemistry
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
Substrate structure
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
37 /00
EC-Blast algorithm/ideas
maximal common subgraph
optimization:
minimal chemical distance, according to
• number of bond changes
• total bond energy change
• number of subgraph fragments determined for a reaction
using “divide and conquer” strategy to map
atoms
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Burkhard Rost
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EC-BLAST flow-chart
SA Rahman, et al. & JM Thornton
(2014) Nat Methods 11:171-4 (Fig. 1)
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
39 /00
EC-BLAST flow-chart
SA Rahman, et al. & JM Thornton
(2014) Nat Methods 11:171-4 (Fig. 1)
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
40 /00
EC-BLAST flow-chart
Bond changes
SA Rahman, et al. & JM Thornton
(2014) Nat Methods 11:171-4
Reaction centres
Substructure
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
41 /00
EC-BLAST changes
SA Rahman, et al. & JM Thornton
(2014) Nat Methods 11:171-4 (Fig. 3a)
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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summary EC-BLAST
Algorithm for quantitative similarity searches
between enzyme reactions at three levels
bond change
reaction center
reaction structure similarity
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Burkhard Rost
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EC-BLAST
Isomerases as a case study
Sergio Martinez Cuesta
et al.
& Janet Thornton
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
44 /00
Isomerases in EC
Classes
Subclasses
EC 1 – Oxidoreductases
5.1 – Racemases and epimerases
EC 2 – Transferases
5.2 – Cis/trans isomerases
EC 3 – Hydrolases
5.3 – Intramolecular oxidoreductases
EC 4 – Lyases
5.4 – Intramolecular transferases
EC 5 – Isomerases
5.5 – Intramolecular lyases
EC 6 - Ligases
5.99 – Other isomerases
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
45 /00
Obtaining change of enzyme function during evolution
Phosophatidylinositol phosphodiesterase superfamily (PIP)
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
46 /00
Changes of isomerase function during evolution
Phosophatidylinositol phosphodiesterase superfamily (PIP)
145 changes distributed across 58 CATH superfamilies
EC 5 ↔ EC 4
Larger than expected
EC 5 ↔ EC 5 20%
EC 5 ↔ Other EC class 80%
A Furnham, et al., CA Orengo & JM Thornton (2012) PLoS Comp Biol 8:e1002403
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
47 /00
Conservation of
chemistry
or
substrate-binding
Comparing all members of each isomerase superfamily
Substrate similarity (%)
Substrates
conserved
+
No conservation
Superfamily average
Chemistry
conserved
Bond change similarity (%)
SA Rahman, et al. & JM Thornton (2014)
Nat Methods
11:171-4
Change
in chemistry
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
48 /00
Correlation of sequence/function evolution
Structural similarity (%)
100
Functional similarity (%)
100
?
0
0
0
100
Sequence identity (%)
0
100
Sequence identity (%)
Chothia and Lesk, 1986
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
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Reaction centre similarity (%)
Sequence vs. isomerase diversity
Comparison
between two
enzymes
r = 0.38
Pairwise sequence identity (%)
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
50 /00
Conclusions – Observations on Enzyme Evolution
Changes in enzyme function during evolution can be
captured from sequence and structure based trees
The study of 276 enzyme superfamilies shows that a
change in substrate, whilst maintaining the same
chemistry, is much more likely than a change in the
chemistry (mechanism) of the enzyme (89%)
Isomerases are different
• More likely to evolve new functions in different EC primary classes
• Exchanges between isomerases and lyases (EC 4) are very common.
The relationship between sequence similarity and
functional similarity in superfamilies is complex, and
there is not a linear relationship.
A Furnham, et al (2012) PLoS Comp Biol 8:e1002403
SA Rahman, et al. & JM Thornton (2014) Nat Methods 11:171-4
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
51 /00
Christine Orengo & colleagues @ UCL
EMBL
© Janet
© Burkhard
Rost Thornton
EMBL-EBI
52 /00
Thanks again to Janet Thornton et al!
© Janet Thornton
EMBL-EBI
© Burkhard Rost
53 /00
Lecture plan (PP2 function)
01: 2014/10/07: no lecture
02: 2014/10/09: welcome: who we are
03: 2014/10/14: no lecture (prof sick)
04: 2014/10/16: no lecture (prof sick)
05: 2014/10/21: no lecture (make-up examen; PP last year)
06: 2014/10/23: Intro - function 1: concepts / homology
07: 2014/10/28: Tobias Hamp: Homology-based prediction of function
08: 2014/10/30: Tobias Hamp: Homology-based prediction of function 2
09: 2014/11/04: no lecture: SVV (student reps)
10: 2014/11/06: Intro - function 3: motifs
11: 2014/11/11: Compute chemistry - enzymatic activity (slides from Janet Thornton)
12: 2014/11/13: Localization 1
13: 2014/11/18: Localization 2 - Tobias Hamp
14: 2014/11/20: Protein-protein interaction 2
15: 2014/11/25: Protein-protein interaction 3
16: 2014/11/27: Protein-DNA/RNA interaction
17: 2014/12/02: SNP effect 1
18: 2014/12/04: no lecture: Dies Academicus
19: 2014/12/09: SNP effect 2
20: 2014/12/11: SNP effect 3 / Marco De Vivo (ISS Genoa) - Drug Design
21: 2014/12/16: Andrea Schafferhans: 3D function prediction
22: 2014/12/18: Andrea Schafferhans: Docking
23-26: no lectures - winter break (2014/12/24 - 2015/01/06)
27: 2015/01/08: Punta - Pfam
28: 2015/01/13: Marco De Vivo (ISS Genoa) - Drug Design
29: 2015/01/15: GO enrichment
30: 2015/01/20: WRAP up !Protein-DNA/RNA interaction 2
31: 2015/01/22: examen
© Burkhard Rost
2015
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