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| Enzyme Name | | Swiss-prot | KEGG |
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| P11447 | P24058 | P04424 |
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| Protein name | Argininosuccinate lyase | Argininosuccinate lyase | Argininosuccinate lyase | argininosuccinate lyasearginosuccinaseargininosuccinic acid lyasearginine-succinate lyaseN-(L-argininosuccinate) arginine-lyaseomega-N-(L-arginino)succinate arginine-lyase2-(omega-N-L-arginino)succinate arginine-lyase (fumarate-forming) |
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| Synonyms | ASALEC 4.3.2.1Arginosuccinase | ASALEC 4.3.2.1ArginosuccinaseDelta-2 crystallinDelta crystallin II | ASALEC 4.3.2.1Arginosuccinase |
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| KEGG pathways | | MAP code | Pathways |
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| MAP00220 | Urea cycle and metabolism of amino groups | | MAP00252 | Alanine and aspartate metabolism | | MAP00330 | Arginine and proline metabolism |
| Swiss-prot:Accession Number | P11447 | P24058 | P04424 |
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| Entry name | ARLY_ECOLI | ARLY2_ANAPL | ARLY_HUMAN |
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| Activity | 2-(N(omega)-L-arginino)succinate = fumarate + L-arginine. | 2-(N(omega)-L-arginino)succinate = fumarate + L-arginine. | 2-(N(omega)-L-arginino)succinate = fumarate + L-arginine. |
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| Subunit |
| Homotetramer. | Homotetramer. |
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| Subcellular location | Cytoplasm (Probable). |
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| Cofactor |
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| References for Catalytic Mechanism | | References | Sections | No. of steps in catalysis |
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| [6] | p.730-732 |
| | [8] | p.14018-14019 |
| | [9] | p.9066-9067 |
| | [10] | Scheme 2, p.333-334 | 3 | | [11] | p.2441-2442 |
| | [12] | p.2427-2429 |
| | [13] | Fig.5, p.1643-1645 | 3 | | [14] | p.2739-2741 |
| | [15] | p.15575 |
| | [16] | Fig.6, p.4173-4174 | 3 | | [18] | Fig.6, p.445-446 |
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| references | | [1] |
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| PubMed ID | 495948 |
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| Journal | Anal Biochem |
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| Year | 1979 |
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| Volume | 95 |
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| Pages | 139-55 |
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| Authors | Murakami-Murofushi K, Ratner S |
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| Title | Argininosuccinase from bovine brain: isolation and comparison of catalytic, physical, and chemical properties with the enzymes from liver and kidney. |
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| [2] |
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| PubMed ID | 6615795 |
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| Journal | Biochemistry |
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| Year | 1983 |
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| Volume | 22 |
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| Pages | 3729-35 |
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| Authors | Garrard LJ, Mathis JM, Raushel FM |
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| Title | Substrate-induced inactivation of argininosuccinate lyase by monofluorofumarate and difluorofumarate. |
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| [3] |
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| PubMed ID | 6722123 |
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| Journal | Biochemistry |
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| Year | 1984 |
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| Volume | 23 |
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| Pages | 1791-5 |
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| Authors | Raushel FM, Garrard LJ |
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| Title | A positional isotope exchange study of the argininosuccinate lyase reaction. |
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| [4] |
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| PubMed ID | 3522565 |
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| Journal | J Biol Chem |
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| Year | 1986 |
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| Volume | 261 |
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| Pages | 8163-6 |
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| Authors | Kim SC, Raushel FM |
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| Title | The determination of enzyme-substrate dissociation rates by dynamic isotope exchange enhancement experiments. |
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| [5] |
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| PubMed ID | 8196062 |
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| Journal | J Mol Biol |
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| Year | 1994 |
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| Volume | 239 |
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| Pages | 336-8 |
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| Authors | Turner MA, Achyuthan AM, Hershfield MS, McInnes RR, Howell PL |
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| Title | Expression, purification, crystallization and preliminary X-ray analysis of human argininosuccinic acid lyase. |
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| [6] |
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| PubMed ID | 7634077 |
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| Journal | Nat Struct Biol |
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| Year | 1994 |
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| Volume | 1 |
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| Pages | 724-34 |
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| Authors | Simpson A, Bateman O, Driessen H, Lindley P, Moss D, Mylvaganam S, Narebor E, Slingsby C |
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| Title | The structure of avian eye lens delta-crystallin reveals a new fold for a superfamily of oligomeric enzymes. |
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| [7] |
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| PubMed ID | 7613869 |
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| Journal | Structure |
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| Year | 1995 |
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| Volume | 3 |
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| Pages | 403-12 |
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| Authors | Simpson A, Moss D, Slingsby C |
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| Title | The avian eye lens protein delta-crystallin shows a novel packing arrangement of tetramers in a supramolecular helix. |
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| [8] |
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| Comments | X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANT ASN-91. |
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| Medline ID | 98039131 |
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| PubMed ID | 9369472 |
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| Journal | Biochemistry |
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| Year | 1997 |
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| Volume | 36 |
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| Pages | 14012-22 |
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| Authors | Abu-Abed M, Turner MA, Vallee F, Simpson A, Slingsby C, Howell PL |
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| Title | Structural comparison of the enzymatically active and inactive forms of delta crystallin and the role of histidine 91. |
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| Related PDB | 1auw |
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| Related Swiss-prot | P24058 |
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| [9] |
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| PubMed ID | 9256435 |
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| Journal | Proc Natl Acad Sci U S A |
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| Year | 1997 |
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| Volume | 94 |
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| Pages | 9063-8 |
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| Authors | Turner MA, Simpson A, McInnes RR, Howell PL |
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| Title | Human argininosuccinate lyase: a structural basis for intragenic complementation. |
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| Related PDB | 1aos |
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| [10] |
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| PubMed ID | 9657972 |
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| Journal | Biochem J |
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| Year | 1998 |
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| Volume | 333 |
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| Pages | 327-34 |
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| Authors | Wu CY, Lee HJ, Wu SH, Chen ST, Chiou SH, Chang GG |
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| Title | Chemical mechanism of the endogenous argininosuccinate lyase activity of duck lens delta2-crystallin. |
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| [11] |
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| PubMed ID | 10029537 |
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| Journal | Biochemistry |
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| Year | 1999 |
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| Volume | 38 |
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| Pages | 2435-43 |
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| Authors | Chakraborty AR, Davidson A, Howell PL |
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| Title | Mutational analysis of amino acid residues involved in argininosuccinate lyase activity in duck delta II crystallin. |
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| [12] |
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| Comments | X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANT ASN-162. |
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| Medline ID | 99155215 |
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| PubMed ID | 10029536 |
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| Journal | Biochemistry |
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| Year | 1999 |
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| Volume | 38 |
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| Pages | 2425-34 |
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| Authors | Vallee F, Turner MA, Lindley PL, Howell PL |
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| Title | Crystal structure of an inactive duck delta II crystallin mutant with bound argininosuccinate. |
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| Related PDB | 1dcn |
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| Related Swiss-prot | P24058 |
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| [13] |
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| PubMed ID | 11092456 |
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| Journal | Cell Mol Life Sci |
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| Year | 2000 |
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| Volume | 57 |
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| Pages | 1637-51 |
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| Authors | Yu B, Howell PL |
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| Title | Intragenic complementation and the structure and function of argininosuccinate lyase. |
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| [14] |
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| PubMed ID | 11258884 |
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| Journal | Biochemistry |
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| Year | 2001 |
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| Volume | 40 |
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| Pages | 2732-42 |
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| Authors | Sampaleanu LM, Vallee F, Slingsby C, Howell PL |
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| Title | Structural studies of duck delta 1 and delta 2 crystallin suggest conformational changes occur during catalysis. |
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| Related PDB | 1hy1,1hy0,1i0a |
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| [15] |
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| PubMed ID | 11747432 |
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| Journal | Biochemistry |
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| Year | 2001 |
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| Volume | 40 |
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| Pages | 15570-80 |
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| Authors | Sampaleanu LM, Vallee F, Thompson GD, Howell PL |
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| Title | Three-dimensional structure of the argininosuccinate lyase frequently complementing allele Q286R. |
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| Related PDB | 1k62 |
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| [16] |
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| PubMed ID | 11698398 |
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| Journal | J Biol Chem |
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| Year | 2002 |
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| Volume | 277 |
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| Pages | 4166-75 |
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| Authors | Sampaleanu LM, Yu B, Howell PL |
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| Title | Mutational analysis of duck delta 2 crystallin and the structure of an inactive mutant with bound substrate provide insight into the enzymatic mechanism of argininosuccinate lyase. |
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| Related PDB | 1k7w |
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| [17] |
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| PubMed ID | 15502303 |
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| Journal | Acta Crystallogr D Biol Crystallogr |
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| Year | 2004 |
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| Volume | 60 |
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| Pages | 1964-70 |
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| Authors | Bhaumik P, Koski MK, Bergmann U, Wierenga RK |
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| Title | Structure determination and refinement at 2.44 A resolution of argininosuccinate lyase from Escherichia coli. |
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| Related PDB | 1tj7 |
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| [18] |
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| PubMed ID | 15320872 |
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| Journal | Biochem J |
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| Year | 2004 |
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| Volume | 384 |
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| Pages | 437-47 |
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| Authors | Sampaleanu LM, Codding PW, Lobsanov YD, Tsai M, Smith GD, Horvatin C, Howell PL |
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| Title | Structural studies of duck delta2 crystallin mutants provide insight into the role of Thr161 and the 280s loop in catalysis. |
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| Related PDB | 1tju,1tjv,1tjw |
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| [19] |
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| PubMed ID | 15362851 |
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| Journal | Biochemistry |
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| Year | 2004 |
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| Volume | 43 |
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| Pages | 11672-82 |
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| Authors | Tsai M, Sampaleanu LM, Greene C, Creagh L, Haynes C, Howell PL |
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| Title | A duck delta1 crystallin double loop mutant provides insight into residues important for argininosuccinate lyase activity. |
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| Related PDB | 1u15,1u16 |
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| comments | There are two delta crystallin isoforms in duck lenses, duck delta1 crystallin (Swissprot; P24057 & PDB;1hy0, 1u15, 1u16) and duck delta2 crystallin (Swissprot; P24057), which are homologous to this enzyme, according to the literature [18]. However, only duck delta2 crystallin (d-delta-c2) is catalytically active (see [18]).
According to the literature [9] & [10], the catalytic reaction of this enzyme proceeds via E1cB-like mechanism. The reaction proceeds as follows (see [14], [16] & [18]):
(1) Glu294 (of PDB;1aos) makes His160 a general acid, by its hydrogen-bond with His160 (also called "charge-relay system").
(2) His160 abstracts a proton from the C-beta of substrate (or deprotonation site of leaving group), leading to formation of a carbanion intermediate, and a conformational change in the active-site loop (280s loop). The negative charge of the intermediate, which must be stabilized by Lys287, may induce the conformational change (see [14], [16] & [18]).
(3) Redistribution of the negative charge in the leaving group (fumarate group) gives an aci-carboxylate intermediate. This intermediate must be stabilized by Lys287, as well.
(4) Ser281 acts as a general acid, which protonates the eliminated group, guanidino group, leading to the cleavage of N1-Calpha bond.
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| created | updated |
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| 2004-06-28 | 2009-02-26 |
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