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2012 - 3D Structures of Biological Macromolecules Part 2: A Case Study in Structural Bioinformatics – C-H…  -Interactions in Proteins. Jürgen Sühnel [email protected] Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena Centre for Bioinformatics Jena / Germany.

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2012 - 3D Structures of Biological Macromolecules

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2012 3d structures of biological macromolecules

  • 2012 -

  • 3D Structuresof Biological Macromolecules

  • Part 2: A Case Study in Structural Bioinformatics –

  • C-H…-Interactions in Proteins

Jürgen Sühnel

[email protected]

Leibniz Institute for Age Research, Fritz Lipmann Institute,

Jena Centre for Bioinformatics

Jena / Germany

Supplementary Material: www.fli-leibniz.de/www_bioc/3D/


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

-system

C

|

H


2012 3d structures of biological macromolecules

C-H...-Interactions:Well-known in smallmolecules

Kooijman et al, Acta Cryst. C. 2000, 56, 481-483

Benzene and analogous compounds

dissolve exothermically in chlorofom.

M. Tamres.

Aromatic compounds as donor molecules in hydrogen bonding.

J. Am. Chem. Soc.1952, 74, 3375-3378.


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

Exceptfor a fewreports on theoccurrenceof

C-H...-interactions in selectedstructures

therehasbeennosystematicstudyforproteins.


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins:Database

Crystal structures with a resolution of 3.0 Å or better

R-factor: 25% or lower

Minimal chain length: 40

Maximum amino acid identity: 25%

PISCES web server


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins: GeometricalSelection

Distance C-X< 4.5 Å

Distance Hp-X < 1.2 Å (aro), 1.0 Å (non-aro)

Angle C-H-X > 120 º


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins: Aims

Analysis of C-H...-interactionsoccurring in proteins

  • Whichinteractionssatisfythegeometricalcriteriaadopted?

  • Whichdonoratomtypesandwhich -systemsareinvolved ?

  • Where in proteins do C-H... -interactionsoccur ?

  • Are thereanysecondarystructureandneighbourhoodrelations ?


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

dCX fraction

< 4.0 Å69%

< 4.1 Å78%

< 4.2 Å86%

< 4.3 Å92%

< 4.4 Å96%

dCX

3.74 – 3.93 Å


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

Donor / acceptorAro- Am- Ac- Arg- Total

C-H 1,832 437 568 712 3,549

(1,01) (0,34) (0,31)(0,99)

Cali-H14,4872,6383,8612,58423,570

(1,95)(0,51)(0,52)(0,88)

Caro-H2,687 361 608 312 3,968

(3,43) (0,66) (0,77) (1,0)

Total19,0063,4365,0373,60831,087

Donors

C-H -total number of aa plus number of Gly

Cali-H -all alipahtic C-H groups except for C-H

Caro-H - all aromatic C-H groups

Acceptors

Aro -aromatic ringHis, Phe, Trp, Tyr

Am -amide groupAsn, Gln

Ac - carboxylate groupAsp, Glu

Arg - amidinium groupArg

Non-redundant database

of 1154 protein chains with 285,794 amino acids


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins


2012 3d structures of biological macromolecules

The 15 interactions identified

occur in all parts of the protein.

Some of them are completely buried

and others are partially exposed

to the solvent.

B-eye-lens-crystallin (1amm, 1.2 Å)


2012 3d structures of biological macromolecules

Interactions are referred to as local

if the sequence distance is smaller

than 10.

41% of C-H...-interactions are local.


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

  • 63% of this interaction type are local.

  • 89% of the –3 peak interactions occur in helices.

  • This interaction may be a major stabilizing element

  • in -helices.


2012 3d structures of biological macromolecules

cytochrome P450 (1bu7)


2012 3d structures of biological macromolecules

L-aminopeptidase D-Ala-esterase/amidase (1b65)


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

M. Brandl, M. S. Weiss, A. Jabs, J. Sühnel, R. Hilgenfeld.

C-H... interactions in proteins.

J. Mol. Biol.2001, 307, 357-377


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

C-H... and C-H...O/N interactions are opportunistic ???


2012 3d structures of biological macromolecules

C-H...-Interactions in Proteins

  • Most prominent are interactions between

    aliphatic or aromatic C-H donors and aromatic acceptors.

  • About three quarters of all Trp-rings, half of all Phe- and Tyr-rings

    and a quarter of His-rings are involved as acceptors in

    C-H...-interactions.

  • On the donor side there is a preference for aromatic C-H groups,

    for prolines and for the long extended aliphatic amino acids

    Lys, Arg and Met.

  • C-H...-interactions involving aromatic groups

    either as donor or as acceptor are found mostly in the interior

    of the protein. The more hydrophilic the participating groups are,

    the closer to the surface are the interactions located.

  • It is likely that C-H...-interactions contribute significantly to

    overall protein stability.

M. Brandl, M. S. Weiss, A. Jabs, J. Sühnel, R. Hilgenfeld.

C-H... interactions in proteins.

J. Mol. Biol.2001, 307, 357-377.


2012 3d structures of biological macromolecules

More Hydrogen Bonds forthe (Structural) Biologist


2012 3d structures of biological macromolecules

More Hydrogen Bonds forthe (Structural) Biologist

A general concept of hydrogen bonding in proteins is emerging.

This concept involves not only N-H and O-H donor groups, but also C-H,

and not only N and O as acceptor groups, but also -systems.

We postulate that the incorporation of the entirety of these

interactions leads to a more complete description of protein structures.

M. S. Weiss, M. Brandl, J. Sühnel, D. Pal, R. Hilgenfeld.

More hydrogen bonds for the (structural) biologist.

Trends Biochem. Sci. 2001, 26, 521-523.


2012 3d structures of biological macromolecules

More Hydrogen Bonds forthe (Structural) Biologist

M. S. Weiss, M. Brandl, J. Sühnel, D. Pal, R. Hilgenfeld.

More hydrogen bonds for the (structural) biologist.

Trends Biochem. Sci. 2001, 26, 521-523.


2012 3d structures of biological macromolecules

More Hydrogen Bonds forthe (Structural) Biologist

phospholipase C (PDB code: 1ah7)

“Classical” N-H...O

(helix192-204)

C-H...O

(LYS153-Val149)

C1-H...

(Trp238-Phe94)

N-H...

(Ser63-Tyr61)

M. S. Weiss, M. Brandl, J. Sühnel, D. Pal, R. Hilgenfeld.

More hydrogen bonds for the (structural) biologist.

Trends Biochem. Sci. 2001, 26, 521-523.


2012 3d structures of biological macromolecules

More Hydrogen Bonds forthe (Structural) Biologist

  • Incorporation of the results obtained in

  • structure prediction and refinement programs

  • Identification of examples for the structural and functional relevance of

  • the new interaction types

M. S. Weiss, M. Brandl, J. Sühnel, D. Pal, R. Hilgenfeld.

More hydrogen bonds for the (structural) biologist.

Trends Biochem. Sci. 2001, 26, 521-523.


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