PDBsum entry 1trh

Hydrolase(carboxylic esterase)

PDB id: 1trh

Contents

Protein chain

534 a.a.

Ligands

NAG ×2

Waters ×301

References listed in PDB file

Key reference

• Title: Two conformational states of candida rugosa lipase.
• Authors: P.Grochulski, Y.Li, J.D.Schrag, M.Cygler.
• Ref.: Protein Sci, 1994, 3, 82-91. [DOI no: 10.1002/pro.5560030111]
• PubMed id: 8142901

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a percentage match of 83%.

Abstract

The structure of Candida rugosa lipase in a new crystal form has been determined and refined at 2.1 A resolution. The lipase molecule was found in an inactive conformation, with the active site shielded from the solvent by a part of the polypeptide chain-the flap. Comparison of this structure with the previously determined "open" form of this lipase, in which the active site is accessible to the solvent and presumably the substrate, shows that the transition between these 2 states requires only movement of the flap. The backbone NH groups forming the putative oxyanion hole do not change position during this rearrangement, indicating that this feature is preformed in the inactive state. The 2 lipase conformations probably correspond to states at opposite ends of the pathway of interfacial activation. Quantitative analysis indicates a large increase of the hydrophobic surface in the vicinity of the active site. The flap undergoes a flexible rearrangement during which some of its secondary structure refolds. The interactions of the flap with the rest of the protein change from mostly hydrophobic in the inactive form to largely hydrophilic in the "open" conformation. Although the flap movement cannot be described as a rigid body motion, it has very definite hinge points at Glu 66 and at Pro 92. The rearrangement is accompanied by a cis-trans isomerization of this proline, which likely increases the energy required for the transition between the 2 states, and may play a role in the stabilization of the active conformation at the water/lipid interface. Carbohydrate attached at Asn 351 also provides stabilization for the open conformation of the flap.

Secondary reference #1

• Title: Insights into interfacial activation from an open structure of candida rugosa lipase.
• Authors: P.Grochulski, Y.Li, J.D.Schrag, F.Bouthillier, P.Smith, D.Harrison, B.Rubin, M.Cygler.
• Ref.: J Biol Chem, 1993, 268, 12843-12847.
• PubMed id: 8509417

Secondary reference #2

• Title: Cloning and analysis of candida cylindracea lipase sequences.
• Authors: M.Lotti, R.Grandori, F.Fusetti, S.Longhi, S.Brocca, A.Tramontano, L.Alberghina.
• Ref.: Gene, 1993, 124, 45-55. [DOI no: 10.1016/0378-1119(93)90760-Z]
• PubMed id: 8440480

Secondary reference #3

• Title: The codon cug is read as serine in an asporogenic yeast candida cylindracea.
• Authors: Y.Kawaguchi, H.Honda, J.Taniguchi-Morimura, S.Iwasaki.
• Ref.: Nature, 1989, 341, 164-166.
• PubMed id: 2506450