1. Primary and tertiary structure of the principal human adenylate kinase
I Von Zabern, B Wittmann-Liebold, R Untucht-Grau, R H Schirmer, E F Pai Eur J Biochem. 1976 Sep;68(1):281-90. doi: 10.1111/j.1432-1033.1976.tb10787.x.
1. Human adenylate kinase (isoenzyme AK-1-1) from skeletal muscle is a single polypeptide chain of 194 amino-acid residues with an acetylmethionine at the N-terminus and a lysine at the C-terminus. 2. The primary structure of the enzyme was determined: Ac-Met-Glu-Glu-Lys-Leu-Lys-Lys-Thr-Lys-Ile-Ile-Phe-Val-Val-Gly-Gly-Pro-Gly-Ser-Gly-Lys-Gly-Thr-Gln-Cys-Glu-Lys-Ile-Val-Gln-Lys-Tyr-Gly-Tyr-Thr-His-Leu-Ser-Thr-Gly-Asp-Leu-Leu-Arg-Ser-Glu-Val-Ser-Ser-Gly-Ser-Ala-Arg-Gly-Lys-Lys-Leu-Ser-Glu-Ile-Met-Glu-Lys-Gly-Gln-Leu-Val-Pro-Leu-Glu-Thr-Val-Leu-Asp-Met-Leu-Arg-Asp-Ala-Met-Val-Ala-Lys-Val-Asn-Thr-Ser-Lys-Gly-Phe-Leu-Ile-Asp-Gly-Tyr-Pro-Arg-Glu-Val-Gln-Gln-Gly-Glu-Glu-Phe-Glu-Arg-Arg-Ile-Gly-Gln-Pro-Thr-Leu-Leu-Leu-Tyr-Val-Asp-Ala-Gly-Pro-Glu-Thr-Met-Thr-Arg-Arg-Leu-Leu-Lys-Arg-Gly-Glu-Thr-Ser-Gly-Arg-Val-Asp-Asn-Glu-Glu-Thr-Ile-Lys-Lys-Arg-Leu-Glu-Thr-Tyr-Tyr-Lys-Ala-Thr-Glu-Pro-Val-Ile-Ala-Phe-Tyr-Glu-Lys-Arg-Gly-Ile-Val-Arg-Lys-Val-Asn-Ala-Glu-Gly-Ser-Val-Asp-Glu-Val-Phe-Ser-Gln-Val-Cys-Thr-His-Leu-Asp-Ala-Leu-Lys. 3. When the primary structure of the human enzyme was fitted to the electron density map of porcine adenylate kinase, all nine amino acids which are different in the homologous enzymes from pig and man were located on the surface of the molecule. 4. Precession photographs of crystalline human and of crystalline porcine adenylate kinase corroborated the result that the polypeptide chains of the two enzymes are folded in a closely related manner. 5. The structure of human adenylate kinase incorporates the so-called nucleotide-binding domain which is present in a wide variety of proteins in nature. Some implications of this phenomenom for the molecular biology and the molecular pharmacology of man are discussed.
2. Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women
Taruna Rajagopal, Arun Seshachalam, Krishna Kumar Rathnam, Srikanth Talluri, Sivaramakrishnan Venkatabalasubramanian, Nageswara Rao Dunna PLoS One. 2022 Jan 21;17(1):e0259761. doi: 10.1371/journal.pone.0259761. eCollection 2022.
Background: Homologous recombination repair (HRR) accurately repairs the DNA double-strand breaks (DSBs) and is crucial for genome stability. Genetic polymorphisms in crucial HRR pathway genes might affect genome stability and promote tumorigenesis. Up to our knowledge, the present study is the first to investigate the impact of HRR gene polymorphisms on BC development in South Indian women. The present population-based case-control study investigated the association of polymorphisms in three key HRR genes (XRCC2-Arg188His, XRCC3-Thr241Met and RAD51-G135C) with BC risk. Materials and methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping the HRR variants in 491 BC cases and 493 healthy women. Results: We observed that the XRCC3 Met allele was significantly associated with BC risk [OR:1.27 (95% CI: 1.02-1.60); p = 0.035]. In addition, the homozygous mutant (C/C) genotype of RAD51 G135C variant conferred 2.19 fold elevated risk of BC [OR: 2.19 (95% CI: 1.06-4.54); p = 0.034]. Stratified analysis of HRR variants and BC clinicopathological features revealed that the XRCC3-Thr241Met and RAD51-G135C variants are associated with BC progression. Combined SNP analysis revealed that the individuals with RAD51-C/C, XRCC2-Arg/Arg, and XRCC3-Thr/Thr genotype combination have three-fold increased BC risk. Conclusion: The present study imparts additional evidence that genetic variants in crucial HRR pathway genes might play a pivotal role in modulating BC risk in South Indian women.
3. Differentiating founder and chronic HIV envelope sequences
John M Murray, Stephen Maher, Talia Mota, Kazuo Suzuki, Anthony D Kelleher, Rob J Center, Damian Purcell PLoS One. 2017 Feb 10;12(2):e0171572. doi: 10.1371/journal.pone.0171572. eCollection 2017.
Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178-346 Asn-Val, 232-236 Thr-Ser, 240-340 Lys-Lys, 279-315 Asp-Lys, 291-792 Ala-Ile, 322-347 Asp-Thr, 535-620 Leu-Asp, 742-837 Arg-Phe, and 750-836 Asp-Ile; the most common optimal pairs for subtype C were 644-781 Lys-Ala (74 of 75 networks), 133-287 Ala-Gln (73/75) and 307-337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553-624 (Ser-Asn), 724-747 (Arg-Arg), or 46-293 (Arg-Glu).
