Functionally relevant motions of haloalkane dehalogenases occur
in the specificity-modulating cap domains

J 2002

Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains

OTYEPKA, Michal a Jiří DAMBORSKÝ

Základní údaje

Originální název

Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains

Autoři

OTYEPKA, Michal (203 Česká republika) a Jiří DAMBORSKÝ (203 Česká republika, garant)

Vydání

Protein Science, 2002, 0961-8368

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.546

Kód RIV

RIV/00216224:14310/02:00006263

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000175141900021

Klíčová slova anglicky

MOLECULAR DYNAMICS; SIMULATION; MOTION; DEHALOGENASE; CATALYSIS

Štítky

CATALYSIS, dehalogenase, molecular dynamics, Motion, simulation

Změněno: 19. 3. 2010 10:54, prof. Mgr. Jiří Damborský, Dr.

Anotace

V originále

One nanosecond molecular dynamics trajectories of three haloalkane dehalogenases (DhlA, LinB and DhaA) are compared. The main domain was rigid in all three dehalogenases, while the substrate specificity-modulating cap domains showed considerably higher mobility. The functionally relevant motions were spread over entire cap domain in DhlA, while were more localized in LinB and DhaA. The highest amplitude of essential motions of DhlA was noted in the alpha4-helix-loop-alpha4-helix region, formerly proposed to participate in the large conformation change needed for product release. The highest amplitude of essential motions of LinB and DhaA was observed in the random coil prior to helix 4 linking two domains of these proteins. This flexibility is the consequence of modular composition of haloalkane dehalogenases. Two members of the catalytic triad, i.e. the nucleophile and the base, showed very high level of rigidity in all three dehalogenases. This rigidity is essential for their function. One of the halide-stabilizing residues, important for the catalysis, shows significantly higher flexibility in DhlA compared to LinB and DhaA. Enhanced flexibility may be required for destabilization of the electrostatic interactions during the release of the halide ion from the deeply buried active site of DhlA. Exchange of water molecules between the enzyme active site and bulk solvent was very different among three dehalogenases. The differences could be related the flexibility of the cap domains and to the number of entrance tunnels.

Návaznosti

LN00A016, projekt VaV

Název: BIOMOLEKULÁRNÍ CENTRUM

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Biomolekulární centrum

Citovat

OTYEPKA, Michal a Jiří DAMBORSKÝ. Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains. Protein Science. 2002, roč. 11, č. 5, s. 1206-1217. ISSN 0961-8368.

@article{404590,
   author = {Otyepka, Michal and Damborský, Jiří},
   article_number = {5},
   keywords = {MOLECULAR DYNAMICS; SIMULATION; MOTION; DEHALOGENASE; CATALYSIS},
   language = {eng},
   issn = {0961-8368},
   journal = {Protein Science},
   title = {Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains},
   url = {http://ncbr.chemi.muni.cz/~jiri/ABSTRACTS/protsci02.html},
   volume = {11},
   year = {2002}
}

TY  - JOUR
ID  - 404590
AU  - Otyepka, Michal - Damborský, Jiří
PY  - 2002
TI  - Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains
JF  - Protein Science
VL  - 11
IS  - 5
SP  - 1206
EP  - 1206
SN  - 09618368
KW  - MOLECULAR DYNAMICS
KW  - SIMULATION
KW  - MOTION
KW  - DEHALOGENASE
KW  - CATALYSIS
UR  - http://ncbr.chemi.muni.cz/~jiri/ABSTRACTS/protsci02.html
N2  - One nanosecond molecular dynamics trajectories of three haloalkane dehalogenases (DhlA, LinB and DhaA) are compared. The main domain was rigid in all three dehalogenases, while the substrate specificity-modulating cap domains showed considerably higher mobility. The functionally relevant motions were spread over entire cap domain in DhlA, while were more localized in LinB and DhaA. The highest amplitude of essential motions of DhlA was noted in the alpha4-helix-loop-alpha4-helix region, formerly proposed to participate in the large conformation change needed for product release. The highest amplitude of essential motions of LinB and DhaA was observed in the random coil prior to helix 4 linking two domains of these proteins. This flexibility is the consequence of modular composition of haloalkane dehalogenases. Two members of the catalytic triad, i.e. the nucleophile and the base, showed very high level of rigidity in all three dehalogenases. This rigidity is essential for their function. One of the halide-stabilizing residues, important for the catalysis, shows significantly higher flexibility in DhlA compared to LinB and DhaA. Enhanced flexibility may be required for destabilization of the electrostatic interactions during the release of the halide ion from the deeply buried active site of DhlA. Exchange of water molecules between the enzyme active site and bulk solvent was very different among three dehalogenases. The differences could be related the flexibility of the cap domains and to the number of entrance tunnels.
ER  -

OTYEPKA, Michal a Jiří DAMBORSKÝ. Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains. \textit{Protein Science}. 2002, roč.~11, č.~5, s.~1206-1217. ISSN~0961-8368.

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