Protein Family Models

This entry represents domain found in diverse homologues of Homocitrate synthase (HCS) [2]. This domain follows the catalytic domain and is required for the enzymatic activity. Paper describing PDB structure 2ztj. [1]. 19996101. Mechanism of substrate recognition and insight into feedback inhibition of homocitrate synthase from Thermus thermophilus. Okada T, Tomita T, Wulandari AP, Kuzuyama T, Nishiyama M;. J Biol Chem. 2010;285:4195-4205. Paper describing PDB structure 3ivs. [2]. 19776021. Crystal structure and functional analysis of homocitrate synthase, an essential enzyme in lysine biosynthesis. Bulfer SL, Scott EM, Couture JF, Pillus L, Trievel RC;. J Biol Chem. 2009;284:35769-35780. Paper describing PDB structure 3rmj. [3]. 22352945. Removal of the C-terminal regulatory domain of alpha-isopropylmalate synthase disrupts functional substrate binding. Huisman FH, Koon N, Bulloch EM, Baker HM, Baker EN, Squire CJ, Parker EJ;. Biochemistry. 2012;51:2289-2297. Paper describing PDB structure 4ov4. [4]. 25128527. Subdomain II of alpha-isopropylmalate synthase is essential for activity: inferring a mechanism of feedback inhibition. Zhang Z, Wu J, Lin W, Wang J, Yan H, Zhao W, Ma J, Ding J, Zhang P, Zhao GP;. J Biol Chem. 2014;289:27966-27978. Paper describing PDB structure 6e1j. [5]. 31023839. Molecular Basis of the Evolution of Methylthioalkylmalate Synthase and the Diversity of Methionine-Derived Glucosinolates. Kumar R, Lee SG, Augustine R, Reichelt M, Vassao DG, Palavalli MH, Allen A, Gershenzon J, Jez JM, Bisht NC;. Plant Cell. 2019;31:1633-1647. (from Pfam)

Date:

2024-10-16

This is the C-terminal regulatory (R) domain of alpha-isopropylmalate synthase, which catalyses the first committed step in the leucine biosynthetic pathway [1]. This domain, is an internally duplicated structure with a novel fold [1]. It comprises two similar units that are arranged such that the two -helices pack together in the centre, crossing at an angle of 34 degrees, sandwiched between the two three-stranded, antiparallel beta-sheets. The overall domain is thus constructed as a beta-alpha-beta three-layer sandwich [1]. [1]. 15159544. Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis. Koon N, Squire CJ, Baker EN;. Proc Natl Acad Sci U S A 2004;101:8295-8300. (from Pfam)

Date:

2024-10-16

This family contains a diverse set of enzymes. These include various aldolases and a region of pyruvate carboxylase. (from Pfam)

Date:

2024-11-05

2-isopropylmalate synthase converts acetyl-CoA and alpha-ketoisovalerate into alpha-isopropylmalate in the committed step of leucine biosynthesis

Date:

2023-03-02

Date:

2021-08-23

This is the first enzyme of leucine biosynthesis. A larger family of homologous proteins includes homocitrate synthase, distinct lineages of 2-isopropylmalate synthase, several distinct, uncharacterized, orthologous sets in the Archaea, and other related enzymes. This model describes a family of 2-isopropylmalate synthases found primarily in Bacteria. The homologous families in the Archaea may represent isozymes and/or related enzymes.

Gene:

leuA

Date:

2021-04-27