PDBsum entry 1l2a

Hydrolase

PDB id: 1l2a

Contents

Protein chains

(+ 0 more) 642 a.a. *

Ligands

BGC-BGC ×6

BGC-BGC-BGC-BGC-BGC-BGC ×6

Waters ×1150

* Residue conservation analysis

PDB id:

1l2a

Name:

Hydrolase

Title:

The crystal structure and catalytic mechanism of cellobiohydrolase cels, the major enzymatic component of the clostridium thermocellum cellulosome

Structure:

Cellobiohydrolase. Chain: a, b, c, d, e, f. Synonym: cellulase ss, endoglucanase ss. Engineered: yes

Source:

Clostridium thermocellum. Organism_taxid: 1515. Gene: cels. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Monomer (from PQS)

Resolution:

2.50Å R-factor: 0.183 R-free: 0.226

Authors:

B.G.Guimaraes,H.Souchon,B.L.Lytle,J.H.D.Wu,P.M.Alzari

Key ref:

B.G.Guimarães et al. (2002). The crystal structure and catalytic mechanism of cellobiohydrolase CelS, the major enzymatic component of the Clostridium thermocellum Cellulosome. J Mol Biol, 320, 587-596. PubMed id: 12096911 DOI: 10.1016/S0022-2836(02)00497-7

Date:

20-Feb-02 Release date: 17-Jul-02

Protein chains

P0C2S5  (GUNS_ACETH) -  Cellulose 1,4-beta-cellobiosidase (reducing end) CelS from Acetivibrio thermocellus

Seq: 741 a.a.

Struc: 642 a.a.

Enzyme reactions

• Enzyme class: E.C.3.2.1.176 - cellulose 1,4-beta-cellobiosidase (reducing end).

DOI no: 10.1016/S0022-2836(02)00497-7

J Mol Biol 320:587-596 (2002)

PubMed id: 12096911

The crystal structure and catalytic mechanism of cellobiohydrolase CelS, the major enzymatic component of the Clostridium thermocellum Cellulosome.

B.G.Guimarães, H.Souchon, B.L.Lytle, J.H.David Wu, P.M.Alzari.

ABSTRACT

Cellobiohydrolase CelS plays an important role in the cellulosome, an active cellulase system produced by the thermophilic anaerobe Clostridium thermocellum. The structures of the catalytic domain of CelS in complex with substrate (cellohexaose) and product (cellobiose) were determined at 2.5 and 2.4 A resolution, respectively. The protein folds into an (alpha/alpha)(6) barrel with a tunnel-shaped substrate-binding region. The conformation of the loops defining the tunnel is intrinsically stable in the absence of substrate, suggesting a model to account for the processive mode of action of family 48 cellobiohydrolases. Structural comparisons with other (alpha/alpha)(6) barrel glycosidases indicate that CelS and endoglucanase CelA, a sequence-unrelated family 8 glycosidase with a groove-shaped substrate-binding region, use the same catalytic machinery to hydrolyze the glycosidic linkage, despite a low sequence similarity and a different endo/exo mode of action. A remarkable feature of the mechanism is the absence, from CelS, of a carboxylic group acting as the base catalyst. The nearly identical arrangement of substrate and functionally important residues in the two active sites strongly suggests an evolutionary relationship between the cellobiohydrolase and endoglucanase families, which can therefore be classified into a new clan of glycoside hydrolases.

Selected figure(s)

Figure 4.
Figure 4. Protein-carbohydrate hydrogen bonding interactions in the CelS-cellohexaose complex. Hydrogen bonds are indicated with broken lines; the corresponding distances are given in Å.

Figure 5.
Figure 5. Structural comparison of family 48 cellobiohydrolase CelS and family 8 endoglucanase CelA. (a) Superposition of the catalytic domains of CelS (green) and CelA (red); bound cellooligomers are shown in CPK mode. (b) Detailed view of the substrate-binding region and the four invariant amino acid residues found in CelS (green) and CelA (red). (c) Amino acid residues and the water nucleophile involved in the catalytic mechanism of CelA and (d) the equivalent view in CelS, including the sugar ring at subsite -1 as seen in CelA (colored in brown). All distances are given in Å.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 320, 587-596) copyright 2002.

Figures were selected by the author.