Structure of bistramide A-actin complex at a 1.35 angstroms resolution

Rizvi SA, Tereshko V, Kossiakoff AA, Kozmin SA

J. Am. Chem. Soc. 2006 Mar;128(12):3882-3

PMID: 16551075


Bistramide A is a highly potent antiproliferative marine natural product from Lissoclinum bistratum. We have previously established actin as the primary cellular receptor of bistramide A. We report herein the X-ray structure of bistramide A bound to monomeric …

Continue reading

The crystal structure of Aq_328 from the hyperthermophilic bacteria Aquifex aeolicus shows an ancestral histone fold

Qiu Y, Tereshko V, Kim Y, Zhang R, Collart F, Yousef M, Kossiakoff A, Joachimiak A

Proteins 2006 Jan;62(1):8-16

PMID: 16287087


The structure of Aq_328, an uncharacterized protein from hyperthermophilic bacteria Aquifex aeolicus, has been determined to 1.9 A by using multi-wavelength anomalous diffraction (MAD) phasing. Although the amino acid sequence analysis shows that …

Continue reading

Alternative views of functional protein binding epitopes obtained by combinatorial shotgun scanning mutagenesis

Pál G, Fong SY, Kossiakoff AA, Sidhu SS

Protein Sci. 2005 Sep;14(9):2405-13

PMID: 16131663


Combinatorial shotgun scanning mutagenesis was used to analyze two large, related protein binding sites to assess the specificity and importance of individual side chain contributions to binding affinity. The strategy allowed for cost-effective generation of a plethora of functional data. …

Continue reading

Shotgun alanine scanning shows that growth hormone can bind productively to its receptor through a drastically minimized interface

Kouadio JL, Horn JR, Pal G, Kossiakoff AA

J. Biol. Chem. 2005 Jul;280(27):25524-32

PMID: 15857837


The high affinity binding site (Site1) of the human growth hormone (hGH) binds to its cognate receptor (hGHR) via a concave surface patch containing about 35 residues. Using 167 sequences from a shotgun alanine scanning analysis of Site1, we …

Continue reading

Total chemical synthesis and X-ray crystal structure of a protein diastereomer: [D-Gln 35]ubiquitin

Bang D, Makhatadze GI, Tereshko V, Kossiakoff AA, Kent SB

Angew. Chem. Int. Ed. Engl. 2005 Jun;44(25):3852-6

PMID: 15834850


Intramolecular cooperativity in a protein binding site assessed by combinatorial shotgun scanning mutagenesis

Pál G, Ultsch MH, Clark KP, Currell B, Kossiakoff AA, Sidhu SS

J. Mol. Biol. 2005 Apr;347(3):489-94

PMID: 15755445


Combinatorial shotgun alanine-scanning was used to assess intramolecular cooperativity in the high affinity site (site 1) of human growth hormone (hGH) for binding to its receptor. A total of 19 side-chains were analyzed and statistically …

Continue reading

The crystal structure of a quercetin 2,3-dioxygenase from Bacillus subtilis suggests modulation of enzyme activity by a change in the metal ion at the active site(s)

Gopal B, Madan LL, Betz SF, Kossiakoff AA

Biochemistry 2005 Jan;44(1):193-201

PMID: 15628860


Common structural motifs, such as the cupin domains, are found in enzymes performing different biochemical functions while retaining a similar active site configuration and structural scaffold. The soil bacterium Bacillus subtilis has 20 cupin genes (0.5% of the total genome) with …

Continue reading

The high- and low-affinity receptor binding sites of growth hormone are allosterically coupled

Walsh ST, Sylvester JE, Kossiakoff AA

Proc. Natl. Acad. Sci. U.S.A. 2004 Dec;101(49):17078-83

PMID: 15563602


Growth hormone regulates its biological properties via a sequential hormone-induced receptor homodimerization mechanism. Using a mutagenesis-scanning analysis of 81 single and 32 pairwise double mutations, we show that the hormone’s two spatially distal receptor binding sites (Site1 and Site2) …

Continue reading

The structural basis for biological signaling, regulation, and specificity in the growth hormone-prolactin system of hormones and receptors

Kossiakoff AA

Adv. Protein Chem. 2004;68:147-69

PMID: 15500861


The pituitary hormones growth hormone (GH), prolactin (PRL) and placental lactogen (PL), are members of an extensive cytokine superfamily of hormones and receptors that share many of the same general structure-function relationships in expressing their biological activities. The biology of the pituitary hormones involves a very …

Continue reading

Dissecting the binding energy epitope of a high-affinity variant of human growth hormone: cooperative and additive effects from combining mutations from independently selected phage display mutagenesis libraries

Bernat B, Sun M, Dwyer M, Feldkamp M, Kossiakoff AA

Biochemistry 2004 May;43(20):6076-84

PMID: 15147191


Phage display mutagenesis is a widely used approach to engineering novel protein properties and is especially powerful in probing structure-function relationships in molecular recognition processes. The relative contributions of additive and cooperative binding forces and the influence of conformational …

Continue reading