Anatomy of enzyme channels.
BACKGROUND
Enzyme active sites can be connected to the exterior environment by one or more channels passing through the protein. Despite our current knowledge of enzyme structure and function, surprisingly little is known about how often channels are present or about any structural features such channels may have in common.


RESULTS
Here, we analyze the long channels (i.e. >15 Å) leading to the active sites of 4,306 enzyme structures. We find that over 64% of enzymes contain two or more long channels, their typical length being 28 Å. We show that amino acid compositions of the channel significantly differ both to the composition of the active site, surface and interior of the protein.


CONCLUSIONS
The majority of enzymes have buried active sites accessible via a network of access channels. This indicates that enzymes tend to have buried active sites, with channels controlling access to, and egress from, them, and that suggests channels may play a key role in helping determine enzyme substrate.
National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, Brno-Bohunice, 625 00, Czech Republic. xpravda@ncbr.muni.cz.
Lukáš
L
Pravda
Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, Olomouc, 771 46, Czech Republic. karel.berka@upol.cz.
Karel
K
Berka
National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, Brno-Bohunice, 625 00, Czech Republic. radka.svobodova@ceitec.muni.cz.
Radka
R
Svobodová Vařeková
National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, Brno-Bohunice, 625 00, Czech Republic. david.sehnal@mail.muni.cz.|Faculty of Informatics, Masaryk University Brno, Botanická 68a, Brno, 602 00, Czech Republic. david.sehnal@mail.muni.cz.
David
D
Sehnal
Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, Olomouc, 771 46, Czech Republic. pavel.banas@upol.cz.
Pavel
P
Banáš
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. roman@ebi.ac.uk.
Roman A
RA
Laskowski
National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, Brno-Bohunice, 625 00, Czech Republic. jaroslav.koca@ceitec.muni.cz.
Jaroslav
J
Koča
Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacký University Olomouc, tř. 17. listopadu 12, Olomouc, 771 46, Czech Republic. michal.otyepka@upol.cz.
Michal
M
Otyepka
D000596:Amino Acids / Q000737:chemistry* / Q000235:genetics; D020134:Catalytic Domain; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008958:Models, Molecular; D011487:Protein Conformation
D000596:Amino Acids; D004798:Enzymes; D007473:Ion Channels