PDBsum entry 1c3c

Lyase

PDB id: 1c3c

Contents

Protein chains

424 a.a. *

Waters ×693

* Residue conservation analysis

PDB id:

1c3c

Name:

Lyase

Title:

T. Maritima adenylosuccinate lyase

Structure:

Protein (adenylosuccinate lyase). Chain: a, b. Engineered: yes

Source:

Thermotoga maritima. Organism_taxid: 2336. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.80Å R-factor: 0.179 R-free: 0.207

Authors:

E.A.Toth,T.O.Yeates

Key ref:

E.A.Toth and T.O.Yeates (2000). The structure of adenylosuccinate lyase, an enzyme with dual activity in the de novo purine biosynthetic pathway. Structure, 8, 163-174. PubMed id: 10673438 DOI: 10.1016/S0969-2126(00)00092-7

Date:

27-Jul-99 Release date: 09-Feb-00

Protein chains

Q9X0I0  (PUR8_THEMA) -  Adenylosuccinate lyase from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 431 a.a.

Struc: 424 a.a.

Enzyme reactions

• Enzyme class: E.C.4.3.2.2 - adenylosuccinate lyase.
• Pathway: Purine Biosynthesis (late stages)
• Reaction:
  1. N₆-(1,2-dicarboxyethyl)-AMP = fumarate + AMP
  2. (2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- carboxamido]succinate = 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4- carboxamide + fumarate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(00)00092-7

Structure 8:163-174 (2000)

PubMed id: 10673438

The structure of adenylosuccinate lyase, an enzyme with dual activity in the de novo purine biosynthetic pathway.

E.A.Toth, T.O.Yeates.

ABSTRACT

Background: Adenylosuccinate lyase is an enzyme that plays a critical role in both cellular replication and metabolism via its action in the de novo purine biosynthetic pathway. Adenylosuccinate lyase is the only enzyme in this pathway to catalyze two separate reactions, enabling it to participate in the addition of a nitrogen at two different positions in adenosine monophosphate. Both reactions catalyzed by adenylosuccinate lyase involve the beta-elimination of fumarate. Enzymes that catalyze this type of reaction belong to a superfamily, the members of which are homotetramers. Because adenylosuccinate lyase plays an integral part in maintaining proper cellular metabolism, mutations in the human enzyme can have severe clinical consequences, including mental retardation with autistic features. Results: The 1.8 A crystal structure of adenylosuccinate lyase from Thermotoga maritima has been determined by multiwavelength anomalous dispersion using the selenomethionine-substituted enzyme. The fold of the monomer is reminiscent of other members of the beta-elimination superfamily. However, its active tetrameric form exhibits striking differences in active-site architecture and cleft size. Conclusions: This first structure of an adenylosuccinate lyase reveals that, along with the catalytic base (His141) and the catalytic acid (His68), Gln212 and Asn270 might play a vital role in catalysis by properly orienting the succinyl moiety of the substrates. We propose a model for the dual activity of adenylosuccinate lyase: a single 180 degrees bond rotation must occur in the substrate between the first and second enzymatic reactions. Modeling of the pathogenic human S413P mutation indicates that the mutation destabilizes the enzyme by disrupting the C-terminal extension.

Selected figure(s)

Figure 8.
Figure 8. Mapping of the S413P human ASL mutation to the T. maritima ASL structure. The residue singled out by directional profiles (Asp406) is colored green. The residue singled out by the extensible threading calculator (ETC) method (Thr404) is colored cyan. The C-terminal extension is colored red. This figure was generated using RIBBONS [36].

The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 163-174) copyright 2000.

Figure was selected by an automated process.